Strain Name:

B6;129P2-Nos2tm1Lau/J

Stock Number:

002596

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Availability:

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Mice homozygous for the Nos2tm1Lau knock-out synthesize Nos2 de novo in response to inflammatory stimuli with production of nitric oxide (NO). This strain may be useful in studies of inflammatory conditions including rheumatoid arthritis, inflammatory bowel disease, cardiac allograft rejection, hepatoxicity, myocardial ischemia-reperfusion and septic shock.

Description

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemHomozygote x Homozygote         (Female x Male)   01-MAR-06
Specieslaboratory mouse
GenerationF39 (25-MAY-11)
Generation Definitions
 
Donating InvestigatorDr. Victor Laubach,   University of Virginia Health Sci. Ctr.

Appearance
black
Related Genotype: a/a

Important Note

Of note, colony managers at The Jackson Laboratory report these mice have a tendency to aggressively barber one another (specifically the whiskers). Attempts to breed away from this characteristic have not been successful to date (June 2009).

Description
Mice homozygous for the Nos2tm1Lau targeted mutation resemble wildtype mice in appearance and histology. Homozygotes are viable and fertile. Unlike Nos1 and Nos3, Nos2 is synthesized de novo in response to a variety of inflammatory stimuli. Induction of Nos2 results in the production of large amounts of nitric oxide (NO) over prolonged periods of time. Excessive NO production has been shown to be beneficial through its antitumor and antimicrobial activities. It is also thought to cause tissue damage and contribute to pathology in a variety of inflammatory conditions including rheumatoid arthritis, inflammatory bowel disease, cardiac allograft rejection, hepatoxicity, myocardial ischemia-reperfusion and septic shock. NO has been demonstrated to play a role in the regulation of blood pressure and hemodynamics. In an LPS-induced model of septic shock, Nos2tm1Lau homozygotes had virtually no serum NO response, but were susceptible to LPS-induced death. Nos2tm1Lau homozygotes exhibit altered responses to M. bovis (BCG), systemic E. coli infection, M. tuberculosis and M.pulmonis. In addition, wound healing properties of fibroblasts are impaired in Nos2tm1Lau homozygotes. Also known as iNOS.

Of note, colony managers at The Jackson Laboratory report these mice have a tendency to aggressively barber one another (specifically the whiskers). Attempts to breed away from this characteristic have not been successful to date (June 2009).

Development
This strain was developed in the laboratory of Dr. Victor Laubach at Glaxo Wellcome Inc. The 129-derived E14TG2a ES cell line was used. The targeting construct was designated as pSPKO-NOS. The ApaI-KpnI fragment containing the calmodulin-binding domain of Nos2 was replaced by the neomycin resistance gene.

Control Information

  Control
   100903 B6129PF2/J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Alzheimer's Disease Models
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008077   129S1/Sv-Bchetm1Loc/J
016198   129S6.Cg-Tg(Camk2a-tTA)1Mmay/JlwsJ
014556   129S6/SvEv-Apoetm4Mae/J
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005708   B6.129-Apbb1tm1Quhu/J
004714   B6.129-Bace1tm1Pcw/J
004098   B6.129-Klc1tm1Gsn/J
004193   B6.129-Psen1tm1Mpm/J
003615   B6.129-Psen1tm1Shn/J
005300   B6.129-Tg(APPSw)40Btla/Mmjax
005617   B6.129P-Psen2tm1Bdes/J
002609   B6.129P2-Nos2tm1Lau/J
007685   B6.129P2-Psen1tm1Vln/J
007999   B6.129P2-Sorl1Gt(Ex255)Byg/J
008087   B6.129S1-Bchetm1Loc/J
002509   B6.129S2-Plautm1Mlg/J
005301   B6.129S2-Tg(APP)8.9Btla/J
004163   B6.129S4-Cdk5r1tm1Lht/J
010959   B6.129S4-Grk5tm1Rjl/J
010960   B6.129S4-Grk5tm2Rjl/J
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006469   B6.129S4-Tg(PSEN1H163R)G9Btla/J
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007251   B6.129X1-Mapttm1Hnd/J
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005642   B6.Cg-Clutm1Jakh/J
005491   B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
009126   B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/Mmjax
005866   B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/Mmjax
008730   B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax
005864   B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
007575   B6.Cg-Tg(CAG-Ngb,-EGFP)1Dgrn/J
016197   B6.Cg-Tg(CAG-OTC/CAT)4033Prab/J
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006006   B6.Cg-Tg(Prnp-APP)A-2Dbo/J
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006394   B6;129-Apba2tm1Sud Apba3tm1Sud Apba1tm1Sud/J
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008476   B6;129-Ncstntm1Sud/J
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007605   B6;129P-Psen1tm1Vln/J
005618   B6;129P2-Bace2tm1Bdes/J
008333   B6;129P2-Dldtm1Ptl/J
003822   B6;129S-Psen1tm1Shn/J
012639   B6;129S4-Mapttm3(HDAC2)Jae/J
012869   B6;129S6-Apbb2tm1Her/J
006410   B6;129S6-Chattm2(cre)Lowl/J
005993   B6;129S6-Pcsk9tm1Jdh/J
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007002   B6;C3-Tg(Prnp-ITM2B/APP695*42)A12Emcg/Mmjax
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000231   B6;C3Fe a/a-Csf1op/J
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005086   C57BL/6-Tg(Camk2a-MME)3Selk/J
008833   C57BL/6-Tg(Camk2a-UBB)3413-1Fwvl/J
007027   C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax
010800   C57BL/6-Tg(Thy1-PTGS2)300Kand/J
010703   C57BL/6-Tg(Thy1-PTGS2)303Kand/J
005706   C57BL/6-Tg(tetO-CDK5R1/GFP)337Lht/J
006618   C57BL/6-Tg(tetO-COX8A/EYFP)1Ksn/J
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View Alzheimer's Disease Models     (109 strains)

Parkinson's Disease Models
005987   129-Achetm1Loc/J
007587   129S-Park2tm1Rpa/J
002779   129S-Parp1tm1Zqw/J
017001   129S.B6N-Plk2tm1Elan/J
016198   129S6.Cg-Tg(Camk2a-tTA)1Mmay/JlwsJ
004608   B6(Cg)-Htra2mnd2/J
021828   B6(SJL)-Lrrk2tm3.1Mjff/J
008133   B6.129-Sncbtm1Sud/J
008084   B6.129P2-Drd4tm1Dkg/J
004744   B6.129P2-Esr1tm1Ksk/J
013586   B6.129P2-Gt(ROSA)26Sortm1Nik/J
002609   B6.129P2-Nos2tm1Lau/J
008843   B6.129P2-Sncgtm1Vlb/J
016566   B6.129S-Hcn1tm2Kndl/J
004322   B6.129S1-Mapk10tm1Flv/J
003190   B6.129S2-Drd2tm1Low/J
006582   B6.129S4-Park2tm1Shn/J
017946   B6.129S4-Pink1tm1Shn/J
005934   B6.129S4-Ucp2tm1Lowl/J
004936   B6.129S6(Cg)-Spp1tm1Blh/J
012453   B6.129X1(FVB)-Lrrk2tm1.1Cai/J
017009   B6.129X1-Nfe2l2tm1Ywk/J
009346   B6.Cg-Lrrk2tm1.1Shn/J
005491   B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
006577   B6.Cg-Park7tm1Shn/J
000567   B6.Cg-T2J +/+ Qkqk-v/J
007004   B6.Cg-Tg(Camk2a-tTA)1Mmay/DboJ
003139   B6.Cg-Tg(DBHn-lacZ)8Rpk/J
007673   B6.Cg-Tg(Gad1-EGFP)3Gfng/J
012466   B6.Cg-Tg(Lrrk2)6Yue/J
012467   B6.Cg-Tg(Lrrk2*G2019S)2Yue/J
008323   B6.Cg-Tg(Mc4r-MAPT/Sapphire)21Rck/J
008321   B6.Cg-Tg(Npy-MAPT/Sapphire)1Rck/J
008324   B6.Cg-Tg(Pmch-MAPT/CFP)1Rck/J
008322   B6.Cg-Tg(Pomc-MAPT/Topaz)1Rck/J
007894   B6.Cg-Tg(Rgs4-EGFP)4Lvt/J
012588   B6.Cg-Tg(TH-ALPP)1Erav/J
012265   B6.Cg-Tg(THY1-SNCA*A30P)TS2Sud/J
008859   B6.Cg-Tg(THY1-SNCA*A53T)F53Sud/J
008135   B6.Cg-Tg(THY1-SNCA*A53T)M53Sud/J
008601   B6.Cg-Tg(Th-cre)1Tmd/J
013583   B6.Cg-Tg(tetO-LRRK2)C7874Cai/J
000544   B6.D2-Cacna1atg/J
012445   B6.FVB-Tg(LRRK2)WT1Mjfa/J
012446   B6.FVB-Tg(LRRK2*G2019S)1Mjfa/J
006660   B6.SJL-Slc6a3tm1.1(cre)Bkmn/J
008364   B6;129-Chattm1(cre/ERT)Nat/J
009688   B6;129-Dbhtm2(Th)Rpa Thtm1Rpa/J
008883   B6;129-Gt(ROSA)26Sortm1(SNCA*A53T)Djmo/TmdJ
008889   B6;129-Gt(ROSA)26Sortm2(SNCA*119)Djmo/TmdJ
008886   B6;129-Gt(ROSA)26Sortm3(SNCA*E46K)Djmo/TmdJ
009347   B6;129-Lrrk2tm1.1Shn/J
016209   B6;129-Lrrk2tm2.1Shn/J
016210   B6;129-Lrrk2tm3.1Shn/J
013050   B6;129-Pink1tm1Aub/J
004807   B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax
006390   B6;129-Sncatm1Sud Sncbtm1.1Sud/J
008532   B6;129-Thtm1(cre/Esr1)Nat/J
008333   B6;129P2-Dldtm1Ptl/J
008333   B6;129P2-Dldtm1Ptl/J
003243   B6;129S-Tnfrsf1atm1Imx Tnfrsf1btm1Imx/J
003692   B6;129X1-Sncatm1Rosl/J
016575   B6;C3-Tg(PDGFB-LRRK2*G2019S)340Djmo/J
016576   B6;C3-Tg(PDGFB-LRRK2*R1441C)574Djmo/J
008169   B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J
004479   B6;C3-Tg(Prnp-SNCA*A53T)83Vle/J
000231   B6;C3Fe a/a-Csf1op/J
012450   B6;D2-Tg(tetO-SNCA)1Cai/J
013725   B6;SJL-Tg(LRRK2)66Mjff/J
008473   B6;SJL-Tg(THY1-SNCA*A30P)M30Sud/J
008134   B6;SJL-Tg(THY1-SNCA*A30P)TS2Sud/J
016976   B6C3-Tg(tetO-SNCA*A53T)33Vle/J
000506   B6C3Fe a/a-Qkqk-v/J
003741   B6D2-Tg(Prnp-MAPT)43Vle/J
024841   B6N.Cg-Tg(Prnp-MAPT*P301S)PS19Vle/J
018768   B6N.Cg-Tg(SNCA*E46K)3Elan/J
012621   C.129S(B6)-Chrna3tm1.1Hwrt/J
016120   C57BL/6-Lrrk1tm1.1Mjff/J
012444   C57BL/6-Lrrk2tm1Mjfa/J
008389   C57BL/6-Tg(THY1-SNCA)1Sud/J
012769   C57BL/6-Tg(Thy1-Sncg)HvP36Putt/J
005706   C57BL/6-Tg(tetO-CDK5R1/GFP)337Lht/J
006618   C57BL/6-Tg(tetO-COX8A/EYFP)1Ksn/J
018785   C57BL/6J-Tg(LRRK2*G2019S)2AMjff/J
018786   C57BL/6J-Tg(LRRK2*R1441G)3IMjff/J
008245   C57BL/6J-Tg(Th-SNCA)5Eric/J
008239   C57BL/6J-Tg(Th-SNCA*A30P*A53T)39Eric/J
016122   C57BL/6N-Lrrk1tm1.1Mjff Lrrk2tm1.1Mjff/J
016121   C57BL/6N-Lrrk2tm1.1Mjff/J
016123   C57BL/6N-Sncatm1Mjff/J
016936   C57BL/6N-Tg(Thy1-SNCA)12Mjff/J
017682   C57BL/6N-Tg(Thy1-SNCA)15Mjff/J
007677   CB6-Tg(Gad1-EGFP)G42Zjh/J
009610   FVB/N-Tg(LRRK2)1Cjli/J
009609   FVB/N-Tg(LRRK2*G2019S)1Cjli/J
009604   FVB/N-Tg(LRRK2*R1441G)135Cjli/J
009090   FVB/NJ-Tg(Slc6a3-PARK2*Q311X)AXwy/J
017678   FVB;129-Pink1tm1Aub Tg(Prnp-SNCA*A53T)AAub/J
017744   FVB;129-Tg(Prnp-SNCA*A53T)AAub/J
010710   FVB;129S6-Sncatm1Nbm Tg(SNCA)1Nbm/J
010788   FVB;129S6-Sncatm1Nbm Tg(SNCA*A30P)1Nbm Tg(SNCA*A30P)2Nbm/J
010799   FVB;129S6-Sncatm1Nbm Tg(SNCA*A53T)1Nbm Tg(SNCA*A53T)2Nbm/J
004808   STOCK Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
000942   STOCK Pitx3ak/2J
014092   STOCK Tg(ACTB-tTA2,-MAPT/lacZ)1Luo/J
006340   STOCK Tg(Gad1-EGFP)98Agmo/J
017000   STOCK Tg(SNCA*E46K)3Elan/J
008474   STOCK Tg(THY1-SNCA*A53T)F53Sud/J
008132   STOCK Tg(THY1-Snca)M1mSud/J
012441   STOCK Tg(tetO-LRRK2*G2019S)E3Cai/J
012442   STOCK Tg(tetO-SNCA*A53T)E2Cai/J
012449   STOCK Tg(teto-LRRK2)C7874Cai/J
View Parkinson's Disease Models     (112 strains)

View Strains carrying   Nos2tm1Lau     (5 strains)

Additional Web Information

Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Hypertension, Essential   (NOS2)
Malaria, Susceptibility to   (NOS2)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Nos2tm1Lau/Nos2tm1Lau

        involves: 129P2/OlaHsd * C57BL/6
  • mortality/aging
  • increased sensitivity to induced morbidity/mortality
    • reduced survival 8 days after 30 minutes of experimentally induced kidney eschemia relative to controls   (MGI Ref ID J:120673)
  • cardiovascular system phenotype
  • *normal* cardiovascular system phenotype
    • blood pressure and heart rate are normal   (MGI Ref ID J:36559)
    • abnormal systemic arterial blood pressure
      • blood pressure drops less in response to LPS injection than it does in controls   (MGI Ref ID J:106197)
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • after injection of platelet-activating factor (PAF), >90% mortality occurs within 30 minutes, similar to wild-type controls   (MGI Ref ID J:113106)
    • pretreatment with wortmannin before PAF treatment confers 100% protection to mutants and wild-type   (MGI Ref ID J:113106)
    • abnormal blood homeostasis   (MGI Ref ID J:120673)
      • decreased circulating leptin level
        • plasma leptin concentrations are significantly reduced   (MGI Ref ID J:94571)
      • increased circulating antidiuretic hormone level
        • elevation in plasma AVP due to LPS injection persists longer than controls, still significantly elevated after 6 hours whereas levels more moderately elevated in controls aftr 4 hours.   (MGI Ref ID J:106197)
      • increased circulating creatinine level
        • higher plasma creatinine levels 24 hours after experimentally induced kidney eschemia than in controls   (MGI Ref ID J:120673)
    • abnormal enzyme/ coenzyme level
      • elevated tissue myeloperoxidase levels relative to controls 9 days after kidney eschemia   (MGI Ref ID J:120673)
    • improved glucose tolerance
      • hyperglycemic in the first 30 minutes of a glucose tolerance test   (MGI Ref ID J:72215)
      • return to fasting glucose levels by 90 minutes when controls are still hyperglycemic   (MGI Ref ID J:72215)
    • increased insulin sensitivity   (MGI Ref ID J:72215)
  • immune system phenotype
  • *normal* immune system phenotype
    • homozygotes are indistinguishable from wild-type in appearance, histology, growth rate, reproduction, and in mortality in an LPS-induced model of septic shock   (MGI Ref ID J:29677)
    • growth of Mycobacterium leprae unaffected   (MGI Ref ID J:64036)
    • normal development of Peyer's patches normal developmentof Peyer's patches   (MGI Ref ID J:80204)
    • abnormal adaptive immunity
      • primary immune responses are unaffected   (MGI Ref ID J:90903)
      • increased T cell proliferation
        • increased T-cell proliferative response to protein antigens   (MGI Ref ID J:90903)
        • "clonal burst size" is unchanged   (MGI Ref ID J:90903)
    • abnormal immune system morphology   (MGI Ref ID J:90903)
      • enlarged inguinal lymph nodes
        • increased cellularity of inguinal lymph nodes   (MGI Ref ID J:90903)
      • increased T cell proliferation
        • increased T-cell proliferative response to protein antigens   (MGI Ref ID J:90903)
        • "clonal burst size" is unchanged   (MGI Ref ID J:90903)
      • increased single-positive T cell number
        • increased numbers of both CD4+ and CD8+ cells in inguinal lymph nodes   (MGI Ref ID J:90903)
    • increased susceptibility to bacterial infection
      • intracellular growth of Mycobacterium tuberculosis and Francisella tularensis is increased but to highly variable extent   (MGI Ref ID J:100513)
    • skin inflammation
      • greatly increased granulomatous inflammation when infected with Mycobacterium leprae   (MGI Ref ID J:64036)
      • resembles borderline tuberculoid lesions of leprosy   (MGI Ref ID J:64036)
  • tumorigenesis
  • altered tumor susceptibility
    • increased rate of growth of ascites tumor cells   (MGI Ref ID J:93780)
    • no apoptosis in ascites tumor cells 2 weeks after innoculation   (MGI Ref ID J:93780)
    • growth of solid tumors from ascites tumor cells is prevented   (MGI Ref ID J:93780)
  • adipose tissue phenotype
  • decreased white adipose tissue amount
    • reduced amounts of epididymal white adipose tissue   (MGI Ref ID J:94571)
  • reproductive system phenotype
  • abnormal fertilization
    • significantly higher numbers of 2-celled embryos produced when homozygotes are intercrossed   (MGI Ref ID J:112824)
    • blastocyst formation is similar to controls   (MGI Ref ID J:112824)
    • fertilization rate of mutant sperm and normal ova is significantly higher than controls   (MGI Ref ID J:112824)
    • fertilization rate of mutant ova and normal sperm is much higher than controls   (MGI Ref ID J:112824)
  • abnormal reproductive system morphology   (MGI Ref ID J:84347)
    • abnormal gametogenesis   (MGI Ref ID J:84347)
      • abnormal male meiosis
        • numbers of pachytene spermatocytes and round spermatids are increased   (MGI Ref ID J:84347)
        • decreased apoptosis of pachytene, early round spermatids at stages I-IV, and diplotene dividing spermatocytes at stages XI-XII   (MGI Ref ID J:84347)
        • reduced heat induced apoptosis   (MGI Ref ID J:84347)
      • abnormal sperm number
        • 65.5% increase in sperm content   (MGI Ref ID J:84347)
    • abnormal testis morphology   (MGI Ref ID J:84347)
      • enlarged seminiferous tubules
        • significantly increased diameter and volume   (MGI Ref ID J:84347)
      • increased testis weight
        • 31% increase   (MGI Ref ID J:84347)
  • endocrine/exocrine gland phenotype
  • abnormal testis morphology   (MGI Ref ID J:84347)
    • enlarged seminiferous tubules
      • significantly increased diameter and volume   (MGI Ref ID J:84347)
    • increased testis weight
      • 31% increase   (MGI Ref ID J:84347)
  • hematopoietic system phenotype
  • increased T cell proliferation
    • increased T-cell proliferative response to protein antigens   (MGI Ref ID J:90903)
    • "clonal burst size" is unchanged   (MGI Ref ID J:90903)
  • increased single-positive T cell number
    • increased numbers of both CD4+ and CD8+ cells in inguinal lymph nodes   (MGI Ref ID J:90903)
  • growth/size/body phenotype
  • increased growth rate
    • experience greater weight gain on a high fat diet   (MGI Ref ID J:72215)
  • behavior/neurological phenotype
  • increased food intake
    • consume 1.6 times as much food as controls on a high fat diet   (MGI Ref ID J:72215)
  • integument phenotype
  • skin inflammation
    • greatly increased granulomatous inflammation when infected with Mycobacterium leprae   (MGI Ref ID J:64036)
    • resembles borderline tuberculoid lesions of leprosy   (MGI Ref ID J:64036)

Nos2tm1Lau/Nos2tm1Lau

        involves: 129P2/OlaHsd * C57BL/6J
  • renal/urinary system phenotype
  • increased urine pH
    • small but significant increase in urine pH and bicarbonate concentration   (MGI Ref ID J:64896)
  • homeostasis/metabolism phenotype
  • increased urine pH
    • small but significant increase in urine pH and bicarbonate concentration   (MGI Ref ID J:64896)

Nos2tm1Lau/Nos2tm1Lau

        B6;129P2-Nos2tm1Lau/J
  • homeostasis/metabolism phenotype
  • decreased circulating alanine transaminase level
    • following hepatic ischemia and reperfusion compared with similarly treated wild-type mice   (MGI Ref ID J:148923)
  • decreased circulating aspartate transaminase level
    • following hepatic ischemia and reperfusion compared with similarly treated wild-type mice   (MGI Ref ID J:148923)
  • decreased susceptibility to injury
    • following hepatic ischemia and reperfusion, mice exhibit reduced liver injury with improved histology due to only mild signs of vascular changes, necrosis, and apoptosis and decreased serum alanine and aspartate transferase levels, and leukocyte (neutrophils, CD3 lymphocytes, CD4 T cells, and granulocytes) recruitment compared with similarly treated wild-type mice   (MGI Ref ID J:148923)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Nos2tm1Lau/Nos2tm1Lau

        B6.129P2-Nos2tm1Lau
  • mortality/aging
  • *normal* mortality/aging
    • better survival after myocardial infarction than for wild-type controls   (MGI Ref ID J:115413)
    • increased mortality induced by ionizing radiation
      • increased sensitivity to ionizing radiation   (MGI Ref ID J:98135)
  • cardiovascular system phenotype
  • *normal* cardiovascular system phenotype
    • unlike mice null for Nos3, ischemia induced retinal neovascularization is not significantly different from controls   (MGI Ref ID J:106207)
    • abnormal heart morphology   (MGI Ref ID J:108269)
      • abnormal heart ventricle morphology
        • hypoxia causes less increase in the RV/LV+Septum ratio than is found in controls   (MGI Ref ID J:108269)
      • abnormal myocardium layer morphology
        • increased hyalination and patchy loss of cross-striations when on 100% oxygen   (MGI Ref ID J:71505)
    • abnormal physiological neovascularization
      • retinal revascularization after ischemia produces small highly branched blood vessels   (MGI Ref ID J:98135)
      • three fold more branching occurs in revascularization than occurs in controls   (MGI Ref ID J:98135)
    • decreased susceptibility to induced choroidal neovascularization
      • choroidal neovascularization following laser-induced rupture of Bruch's membrane is reduced   (MGI Ref ID J:106207)
    • decreased systemic arterial systolic blood pressure
      • more significant drop in systolic blood pressure after myocardial infarction than is seen in controls   (MGI Ref ID J:104749)
    • increased left ventricle developed pressure
      • left ventricular maximum developed pressure was similar to sham operated animals 4 months after myocardial infarction rather than being reduced as in wild-type controls   (MGI Ref ID J:115413)
  • vision/eye phenotype
  • decreased susceptibility to induced choroidal neovascularization
    • choroidal neovascularization following laser-induced rupture of Bruch's membrane is reduced   (MGI Ref ID J:106207)
  • nervous system phenotype
  • abnormal central nervous system regeneration
    • recover better from compression injury to the spinal cord than do controls, severity of behavioral deficit due to injury is somewhat less   (MGI Ref ID J:110081)
  • abnormal corpus callosum morphology
    • increased myelin pathology after treatment with cuprizone   (MGI Ref ID J:125459)
  • decreased oligodendrocyte number
    • decreased numbers of mature oligodendrocytes after cuprizone treatment   (MGI Ref ID J:125459)
    • numbers of oligodendrocytes reduced to 50% of controls after 3.5 weeks   (MGI Ref ID J:125459)
    • undergo increased apoptosis which is not seen for microglia and astrocytes   (MGI Ref ID J:125459)
  • increased susceptibility to pharmacologically induced seizures
    • shortened latency to seizures induced by kainic acid when on a normal diet   (MGI Ref ID J:107300)
    • behavior responses correspond to grade V seizures   (MGI Ref ID J:107300)
    • latency to seizure is prolonged when fed a ketogenic diet   (MGI Ref ID J:107300)
  • digestive/alimentary phenotype
  • decreased susceptibility to induced colitis
    • less susceptibility to dextran sodium sulfate induced colitis   (MGI Ref ID J:87601)
    • less severe weight loss, blood loss and macroscopic damage   (MGI Ref ID J:87601)
    • improved survival   (MGI Ref ID J:87601)
  • homeostasis/metabolism phenotype
  • abnormal blood coagulation
    • shorter time to thrombus formation and vessel occlusion   (MGI Ref ID J:117987)
    • abnormal platelet physiology
      • increased platelet deposition   (MGI Ref ID J:117987)
  • abnormal glucose homeostasis
    • no effect on streptozotocin induced diabetis   (MGI Ref ID J:95957)
  • enhanced wound healing
    • recover better from compression injury to the spinal cord than do controls, severity of behavioral deficit due to injury is somewhat less   (MGI Ref ID J:110081)
  • increased mortality induced by ionizing radiation
    • increased sensitivity to ionizing radiation   (MGI Ref ID J:98135)
  • behavior/neurological phenotype
  • abnormal eating behavior
    • inhibitory effect of insulin on feeding is enhanced by 10 -8M TNF alpha   (MGI Ref ID J:112153)
  • abnormal frequency of paradoxical sleep
    • significantly more time spent in REM sleep during the light period   (MGI Ref ID J:83571)
    • increased REM sleep results from more REM episodes and shortened periods in between   (MGI Ref ID J:83571)
    • more non REM sleep episodes in light period but of shorter duration   (MGI Ref ID J:83571)
    • significantly less non REM sleep during dark periods   (MGI Ref ID J:83571)
  • increased susceptibility to pharmacologically induced seizures
    • shortened latency to seizures induced by kainic acid when on a normal diet   (MGI Ref ID J:107300)
    • behavior responses correspond to grade V seizures   (MGI Ref ID J:107300)
    • latency to seizure is prolonged when fed a ketogenic diet   (MGI Ref ID J:107300)
  • respiratory system phenotype
  • *normal* respiratory system phenotype
    • alveolar fluid clearance unaffected by amilorid and forskolin which both affect clearance in controls   (MGI Ref ID J:71505)
    • abnormal respiratory bronchiole morphology
      • increased ulceration in 100% oxygen than seen with controls   (MGI Ref ID J:71505)
    • abnormal respiratory system physiology
      • reduced lung injury relative to controls after 55 hours at 100% oxygen   (MGI Ref ID J:71505)
  • immune system phenotype
  • abnormal osteoclast morphology
    • elevated osteoclast surface to bone surface in comparison to controls 7 days after bone reloading   (MGI Ref ID J:112399)
  • decreased susceptibility to induced colitis
    • less susceptibility to dextran sodium sulfate induced colitis   (MGI Ref ID J:87601)
    • less severe weight loss, blood loss and macroscopic damage   (MGI Ref ID J:87601)
    • improved survival   (MGI Ref ID J:87601)
  • hematopoietic system phenotype
  • abnormal osteoclast morphology
    • elevated osteoclast surface to bone surface in comparison to controls 7 days after bone reloading   (MGI Ref ID J:112399)
  • abnormal platelet physiology
    • increased platelet deposition   (MGI Ref ID J:117987)
  • skeleton phenotype
  • abnormal bone mineralization
    • lower mineral aposition rate than in controls 7 days after bone reloading   (MGI Ref ID J:112399)
  • abnormal bone structure
    • less recovery of lost bone volume due to bone unloading 7 days after reloading   (MGI Ref ID J:112399)
    • abnormal osteoclast morphology
      • elevated osteoclast surface to bone surface in comparison to controls 7 days after bone reloading   (MGI Ref ID J:112399)

Nos2tm1Lau/Nos2tm1Lau

        B6.129P2-Nos2tm1Lau/J
  • respiratory system phenotype
  • abnormal surfactant physiology
    • following infection with mycoplasma, the numbers of large surfactant aggregates is decreased and higher protein to lipid ratios are present in the bronchoalveolare lavage fluid compared to similarly infected wild-type mice   (MGI Ref ID J:130520)
    • following infection with mycoplasma, the minimal surface area on the pulsating bubble is increased and the levels of surfactant protein are decreased compared to similarly infected wild-type mice   (MGI Ref ID J:130520)
  • behavior/neurological phenotype
  • abnormal circadian rhythm
    • mice display a more pronounced diurnal variation of sleep-wake activity   (MGI Ref ID J:83571)
  • abnormal sleep pattern
    • mice spend more time in REM sleep during the light phase as a result of an increased number of REM episodes and shortened duration of the inter REM intervals   (MGI Ref ID J:83571)
    • mice display a more pronounced diurnal variation of sleep-wake activity   (MGI Ref ID J:83571)
    • mice spend less time in non-REM sleep during the dark phase   (MGI Ref ID J:83571)
    • during the light phase mice spend the same amount of time in non-REM sleep but have a higher number of non-REM episodes of shorter average duration   (MGI Ref ID J:83571)
  • nervous system phenotype
  • abnormal brain wave pattern
    • during non-REM sleep the absolute value of slow wave activity is increased   (MGI Ref ID J:83571)
  • immune system phenotype
  • abnormal inflammatory response
    • unlike in wild-type mice, LPS injection fails to reduce nighttime body temperature relative to saline injected controls   (MGI Ref ID J:103018)
    • decreased inflammatory response
      • fever in response to LPS injection is partially reduced compared to wild-type controls   (MGI Ref ID J:103018)
      • the fever response to LPS is initiated but not sustained   (MGI Ref ID J:103018)
      • however, fever in response to turpentine injection is not different from controls   (MGI Ref ID J:103018)

Nos2tm1Lau/Nos2tm1Lau

        involves: 129P2/OlaHsd
  • immune system phenotype
  • *normal* immune system phenotype
    • unlike in mice null for Nos1 or Nos3, no abnormalities in leukocyte rolling or adhesion are detected   (MGI Ref ID J:55936)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Neurobiology Research
Parkinson's Disease
      resistance to MPTP

Nos2tm1Lau related

Immunology, Inflammation and Autoimmunity Research
Inflammation
      Inflammatory bowel disease

Neurobiology Research
Alzheimer's Disease

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Nos2tm1Lau
Allele Name targeted mutation 1, Victor E Laubach
Allele Type Targeted (Null/Knockout)
Common Name(s) NOS2-; NOS2tm/Lau; Nos2tm1Lau; iNOS KO; iNOS-;
Mutation Made ByDr. Victor Laubach,   University of Virginia Health Sci. Ctr.
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14TG2a
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name Nos2, nitric oxide synthase 2, inducible
Chromosome 11
Gene Common Name(s) HEP-NOS; INOS; NOS; NOS-II; NOS2A; Nos-2; nitric oxide synthase-2 (brain);
Molecular Note A neomycin cassette replaced exons 12 and 13 of the gene, which encode the calmodulin-binding domain. Northern and Western blots of IFNg/LPS-stimulated peritoneal macrophages showed no detectable Nos2 mRNA or protein, respectively. [MGI Ref ID J:183641] [MGI Ref ID J:29677]

Genotyping

Genotyping Information

Genotyping Protocols

Nos2tm1Lau, Melt Curve Analysis
Nos2tm1Lau, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Laubach VE; Shesely EG; Smithies O; Sherman PA. 1995. Mice lacking inducible nitric oxide synthase are not resistant to lipopolysaccharide-induced death. Proc Natl Acad Sci U S A 92(23):10688-92. [PubMed: 7479866]  [MGI Ref ID J:29677]

Additional References

Guo Y; Jones WK; Xuan YT; Tang XL; Bao W; Wu WJ; Han H; Laubach VE; Ping P; Yang Z; Qiu Y; Bolli R. 1999. The late phase of ischemic preconditioning is abrogated by targeted disruption of the inducible NO synthase gene [see comments] Proc Natl Acad Sci U S A 96(20):11507-12. [PubMed: 10500207]  [MGI Ref ID J:57975]

Kisley LR; Barrett BS; Bauer AK; Dwyer-Nield LD; Barthel B; Meyer AM; Thompson DC; Malkinson AM. 2002. Genetic ablation of inducible nitric oxide synthase decreases mouse lung tumorigenesis. Cancer Res 62(23):6850-6. [PubMed: 12460898]  [MGI Ref ID J:80325]

Rivera J; Mukherjee J; Weiss LM; Casadevall A. 2002. Antibody Efficacy in Murine Pulmonary Cryptococcus neoformans Infection: A Role for Nitric Oxide. J Immunol 168(7):3419-27. [PubMed: 11907100]  [MGI Ref ID J:75578]

Nos2tm1Lau related

Abu-Ghanem Y; Cohen H; Buskila Y; Grauer E; Amitai Y. 2008. Enhanced stress reactivity in nitric oxide synthase type 2 mutant mice: findings in support of astrocytic nitrosative modulation of behavior. Neuroscience 156(2):257-65. [PubMed: 18723080]  [MGI Ref ID J:141014]

Adams LB; Job CK; Krahenbuhl JL. 2000. Role of inducible nitric oxide synthase in resistance to Mycobacterium leprae in mice. Infect Immun 68(9):5462-5. [PubMed: 10948185]  [MGI Ref ID J:64036]

Aheng C; Ly N; Kelly M; Ibrahim S; Ricquier D; Alves-Guerra MC; Miroux B. 2011. Deletion of UCP2 in iNOS deficient mice reduces the severity of the disease during experimental autoimmune encephalomyelitis. PLoS One 6(8):e22841. [PubMed: 21857957]  [MGI Ref ID J:176503]

Ahn B; Ohshima H. 2001. Suppression of intestinal polyposis in Apc(Min/+) mice by inhibiting nitric oxide production. Cancer Res 61(23):8357-60. [PubMed: 11731407]  [MGI Ref ID J:73152]

Akita Y; Otani H; Matsuhisa S; Kyoi S; Enoki C; Hattori R; Imamura H; Kamihata H; Kimura Y; Iwasaka T. 2007. Exercise-induced activation of cardiac sympathetic nerve triggers cardioprotection via redox-sensitive activation of eNOS and upregulation of iNOS. Am J Physiol Heart Circ Physiol 292(5):H2051-9. [PubMed: 17259438]  [MGI Ref ID J:125942]

Al Gadban MM; German J; Truman JP; Soodavar F; Riemer EC; Twal WO; Smith KJ; Heller D; Hofbauer AF; Oates JC; Hammad SM. 2012. Lack of nitric oxide synthases increases lipoprotein immune complex deposition in the aorta and elevates plasma sphingolipid levels in lupus. Cell Immunol 276(1-2):42-51. [PubMed: 22560558]  [MGI Ref ID J:188295]

Anand RJ; Dai S; Rippel C; Leaphart C; Qureshi F; Gribar SC; Kohler JW; Li J; Stolz DB; Sodhi C; Hackam DJ. 2008. Activated macrophages inhibit enterocyte gap junctions via the release of nitric oxide. Am J Physiol Gastrointest Liver Physiol 294(1):G109-19. [PubMed: 17975131]  [MGI Ref ID J:130509]

Ando A; Yang A; Mori K; Yamada H; Yamada E; Takahashi K; Saikia J; Kim M; Melia M; Fishman M; Huang P; Campochiaro PA. 2002. Nitric oxide is proangiogenic in the retina and choroid. J Cell Physiol 191(1):116-24. [PubMed: 11920687]  [MGI Ref ID J:106207]

Andrade RM; Portillo JA; Wessendarp M; Subauste CS. 2005. CD40 signaling in macrophages induces activity against an intracellular pathogen independently of gamma interferon and reactive nitrogen intermediates. Infect Immun 73(5):3115-23. [PubMed: 15845519]  [MGI Ref ID J:97614]

Arantes RM; Marche HH; Bahia MT; Cunha FQ; Rossi MA; Silva JS. 2004. Interferon-gamma-induced nitric oxide causes intrinsic intestinal denervation in Trypanosoma cruzi-infected mice. Am J Pathol 164(4):1361-8. [PubMed: 15039223]  [MGI Ref ID J:89108]

Arnett HA; Hellendall RP; Matsushima GK; Suzuki K; Laubach VE; Sherman P; Ting JP. 2002. The protective role of nitric oxide in a neurotoxicant-induced demyelinating model. J Immunol 168(1):427-33. [PubMed: 11751989]  [MGI Ref ID J:125459]

Bandeira M; Santos CS; de Azevedo EC; Soares LM; Macedo JO; Marchi S; da Silva CL; Chagas-Junior AD; McBride AJ; McBride FW; Reis MG; Athanazio DA. 2011. Attenuated Nephritis in Inducible Nitric Oxide Synthase Knockout C57BL/6 Mice and Pulmonary Hemorrhage in CB17 SCID and Recombination Activating Gene 1 Knockout C57BL/6 Mice Infected with Leptospira interrogans. Infect Immun 79(7):2936-40. [PubMed: 21576342]  [MGI Ref ID J:173478]

Bartholdy C; Nansen A; Christensen JE; Marker O; Thomsen AR. 1999. Inducible nitric-oxide synthase plays a minimal role in lymphocytic choriomeningitis virus-induced, T cell-mediated protective immunity and immunopathology. J Gen Virol 80(Pt 11):2997-3005. [PubMed: 10580062]  [MGI Ref ID J:103345]

Bast A; Erttmann SF; Walther R; Steinmetz I. 2010. Influence of iNOS and COX on peroxiredoxin gene expression in primary macrophages. Free Radic Biol Med 49(12):1881-91. [PubMed: 20869433]  [MGI Ref ID J:167094]

Becerril S; Rodriguez A; Catalan V; Sainz N; Ramirez B; Collantes M; Penuelas I; Gomez-Ambrosi J; Fruhbeck G. 2010. Deletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function. PLoS One 5(6):e10962. [PubMed: 20532036]  [MGI Ref ID J:161815]

Beck PL; Li Y; Wong J; Chen CW; Keenan CM; Sharkey KA; McCafferty DM. 2007. Inducible nitric oxide synthase from bone marrow-derived cells plays a critical role in regulating colonic inflammation. Gastroenterology 132(5):1778-90. [PubMed: 17449036]  [MGI Ref ID J:128325]

Beck PL; Xavier R; Wong J; Ezedi I; Mashimo H; Mizoguchi A; Mizoguchi E; Bhan AK; Podolsky DK. 2004. Paradoxical roles of different nitric oxide synthase isoforms in colonic injury. Am J Physiol Gastrointest Liver Physiol 286(1):G137-47. [PubMed: 14665440]  [MGI Ref ID J:87601]

Beisiegel M; Mollenkopf HJ; Hahnke K; Koch M; Dietrich I; Reece ST; Kaufmann SH. 2009. Combination of host susceptibility and Mycobacterium tuberculosis virulence define gene expression profile in the host. Eur J Immunol 39(12):3369-84. [PubMed: 19795415]  [MGI Ref ID J:155483]

Bhandari V; Choo-Wing R; Harijith A; Sun H; Syed MA; Homer RJ; Elias JA. 2012. Increased hyperoxia-induced lung injury in nitric oxide synthase 2 null mice is mediated via angiopoietin 2. Am J Respir Cell Mol Biol 46(5):668-76. [PubMed: 22227562]  [MGI Ref ID J:196034]

Blanchard TG; Yu F; Hsieh CL; Redline RW. 2003. Severe inflammation and reduced bacteria load in murine helicobacter infection caused by lack of phagocyte oxidase activity. J Infect Dis 187(10):1609-15. [PubMed: 12721941]  [MGI Ref ID J:120653]

Blyszczuk P; Berthonneche C; Behnke S; Glonkler M; Moch H; Pedrazzini T; Luscher TF; Eriksson U; Kania G. 2013. Nitric oxide synthase 2 is required for conversion of pro-fibrogenic inflammatory CD133(+) progenitors into F4/80(+) macrophages in experimental autoimmune myocarditis. Cardiovasc Res 97(2):219-29. [PubMed: 23090609]  [MGI Ref ID J:210288]

Bokhari SM; Kim KJ; Pinson DM; Slusser J; Yeh HW; Parmely MJ. 2008. NK cells and gamma interferon coordinate the formation and function of hepatic granulomas in mice infected with the Francisella tularensis live vaccine strain. Infect Immun 76(4):1379-89. [PubMed: 18227174]  [MGI Ref ID J:133531]

Boyer L; Plantier L; Dagouassat M; Lanone S; Goven D; Caramelle P; Berrehar F; Kerbrat S; Dinh-Xuan AT; Crestani B; Le Gouvello S; Boczkowski J. 2011. Role of nitric oxide synthases in elastase-induced emphysema. Lab Invest 91(3):353-62. [PubMed: 20956973]  [MGI Ref ID J:169267]

Brahmachari S; Pahan K. 2010. Myelin basic protein priming reduces the expression of Foxp3 in T cells via nitric oxide. J Immunol 184(4):1799-809. [PubMed: 20083653]  [MGI Ref ID J:159486]

Brahmachari S; Pahan K. 2009. Suppression of regulatory T cells by IL-12p40 homodimer via nitric oxide. J Immunol 183(3):2045-58. [PubMed: 19587012]  [MGI Ref ID J:151706]

Bratt JM; Franzi LM; Linderholm AL; Last MS; Kenyon NJ; Last JA. 2009. Arginase enzymes in isolated airways from normal and nitric oxide synthase 2-knockout mice exposed to ovalbumin. Toxicol Appl Pharmacol 234(3):273-80. [PubMed: 19027033]  [MGI Ref ID J:145875]

Breitbach K; Klocke S; Tschernig T; van Rooijen N; Baumann U; Steinmetz I. 2006. Role of Inducible Nitric Oxide Synthase and NADPH Oxidase in Early Control of Burkholderia pseudomallei Infection in Mice. Infect Immun 74(11):6300-6309. [PubMed: 17000727]  [MGI Ref ID J:113561]

Brumshagen C; Maus R; Bischof A; Ueberberg B; Bohling J; Osterholzer JJ; Ogunniyi AD; Paton JC; Welte T; Maus UA. 2012. FMS-like tyrosine kinase 3 ligand treatment of mice aggravates acute lung injury in response to Streptococcus pneumoniae: role of pneumolysin. Infect Immun 80(12):4281-90. [PubMed: 23006850]  [MGI Ref ID J:190619]

Buhtoiarov IN; Lum HD; Berke G; Sondel PM; Rakhmilevich AL. 2006. Synergistic activation of macrophages via CD40 and TLR9 results in T cell independent antitumor effects. J Immunol 176(1):309-18. [PubMed: 16365423]  [MGI Ref ID J:126263]

Burrer R; Buchmeier MJ; Wolfe T; Ting JP; Feuer R; Iglesias A; von Herrath MG. 2007. Exacerbated pathology of viral encephalitis in mice with central nervous system-specific autoantibodies. Am J Pathol 170(2):557-66. [PubMed: 17255324]  [MGI Ref ID J:117906]

Buskila Y; Abu-Ghanem Y; Levi Y; Moran A; Grauer E; Amitai Y. 2007. Enhanced astrocytic nitric oxide production and neuronal modifications in the neocortex of a NOS2 mutant mouse. PLoS ONE 2(9):e843. [PubMed: 17786214]  [MGI Ref ID J:129384]

Buxbaum LU; Uzonna JE; Goldschmidt MH; Scott P. 2002. Control of New World cutaneous leishmaniasis is IL-12 independent but STAT4 dependent. Eur J Immunol 32(11):3206-15. [PubMed: 12555666]  [MGI Ref ID J:115538]

Cambien B; Bergmeier W; Saffaripour S; Mitchell HA; Wagner DD. 2003. Antithrombotic activity of TNF-alpha. J Clin Invest 112(10):1589-96. [PubMed: 14617760]  [MGI Ref ID J:117987]

Carnio EC; Stabile AM; Batalhao ME; Silva JS; Antunes-Rodrigues J; Branco LG; Magder S. 2005. Vasopressin release during endotoxaemic shock in mice lacking inducible nitric oxide synthase. Pflugers Arch 450(6):390-4. [PubMed: 15971084]  [MGI Ref ID J:106197]

Cauwels A; Janssen B; Buys E; Sips P; Brouckaert P. 2006. Anaphylactic shock depends on PI3K and eNOS-derived NO. J Clin Invest 116(8):2244-51. [PubMed: 16886062]  [MGI Ref ID J:113106]

Cauwels A; Van Molle W; Janssen B; Everaerdt B; Huang P; Fiers W; Brouckaert P. 2000. Protection against TNF-induced lethal shock by soluble guanylate cyclase inhibition requires functional inducible nitric oxide synthase. Immunity 13(2):223-31. [PubMed: 10981965]  [MGI Ref ID J:64176]

Cha HN; Kim YW; Kim JY; Kim YD; Song IH; Min KN; Park SY. 2010. Lack of inducible nitric oxide synthase does not prevent aging-associated insulin resistance. Exp Gerontol 45(9):711-8. [PubMed: 20493940]  [MGI Ref ID J:164264]

Chan JY; Cooney GJ; Biden TJ; Laybutt DR. 2011. Differential regulation of adaptive and apoptotic unfolded protein response signalling by cytokine-induced nitric oxide production in mouse pancreatic beta cells. Diabetologia 54(7):1766-76. [PubMed: 21472432]  [MGI Ref ID J:172611]

Charbonneau A; Marette A. 2010. Inducible nitric oxide synthase induction underlies lipid-induced hepatic insulin resistance in mice: potential role of tyrosine nitration of insulin signaling proteins. Diabetes 59(4):861-71. [PubMed: 20103705]  [MGI Ref ID J:164330]

Chatterjee S; Lardinois O; Bonini MG; Bhattacharjee S; Stadler K; Corbett J; Deterding LJ; Tomer KB; Kadiiska M; Mason RP. 2009. Site-specific carboxypeptidase B1 tyrosine nitration and pathophysiological implications following its physical association with nitric oxide synthase-3 in experimental sepsis. J Immunol 183(6):4055-66. [PubMed: 19717511]  [MGI Ref ID J:152293]

Chauhan SD; Seggara G; Vo PA; Macallister RJ; Hobbs AJ; Ahluwalia A. 2003. Protection against lipopolysaccharide-induced endothelial dysfunction in resistance and conduit vasculature of iNOS knockout mice. FASEB J 17(6):773-5. [PubMed: 12586741]  [MGI Ref ID J:118016]

Chen L; Majde JA; Krueger JM. 2003. Spontaneous sleep in mice with targeted disruptions of neuronal or inducible nitric oxide synthase genes. Brain Res 973(2):214-22. [PubMed: 12738065]  [MGI Ref ID J:83571]

Chen L; Taishi P; Duricka D; Krueger JM. 2004. Brainstem prolactin mRNA is enhanced in mice with suppressed neuronal nitric oxide synthase activity. Brain Res Mol Brain Res 129(1-2):179-84. [PubMed: 15469894]  [MGI Ref ID J:115454]

Chen L; Taishi P; Majde JA; Peterfi Z; Obal F Jr; Krueger JM. 2004. The role of nitric oxide synthases in the sleep responses to tumor necrosis factor-alpha. Brain Behav Immun 18(4):390-8. [PubMed: 15157956]  [MGI Ref ID J:105452]

Chiang E; Dang O; Anderson K; Matsuzawa A; Ichijo H; David M. 2006. Cutting edge: apoptosis-regulating signal kinase 1 is required for reactive oxygen species-mediated activation of IFN regulatory factor 3 by lipopolysaccharide. J Immunol 176(10):5720-4. [PubMed: 16670275]  [MGI Ref ID J:131688]

Choi KS; Song EK; Yim CY. 2008. Cytokines secreted by IL-2-activated lymphocytes induce endogenous nitric oxide synthesis and apoptosis in macrophages. J Leukoc Biol 83(6):1440-50. [PubMed: 18339892]  [MGI Ref ID J:136847]

Chyu KY; Dimayuga P; Zhu J; Nilsson J; Kaul S; Shah PK; Cercek B. 1999. Decreased neointimal thickening after arterial wall injury in inducible nitric oxide synthase knockout mice. Circ Res 85(12):1192-8. [PubMed: 10590247]  [MGI Ref ID J:59834]

Cohen O; Ish-Shalom E; Kfir-Erenfeld S; Herr I; Yefenof E. 2012. Nitric oxide and glucocorticoids synergize in inducing apoptosis of CD4(+)8(+) thymocytes: implications for 'Death by Neglect' and T-cell function. Int Immunol 24(12):783-91. [PubMed: 22949567]  [MGI Ref ID J:190546]

Cole C; Thomas S; Filak H; Henson PM; Lenz LL. 2012. Nitric oxide increases susceptibility of Toll-like receptor-activated macrophages to spreading Listeria monocytogenes. Immunity 36(5):807-20. [PubMed: 22542147]  [MGI Ref ID J:187324]

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Watanuki M; Sakai A; Sakata T; Tsurukami H; Miwa M; Uchida Y; Watanabe K; Ikeda K; Nakamura T. 2002. Role of inducible nitric oxide synthase in skeletal adaptation to acute increases in mechanical loading. J Bone Miner Res 17(6):1015-25. [PubMed: 12054156]  [MGI Ref ID J:112399]

Weberpals M; Hermes M; Hermann S; Kummer MP; Terwel D; Semmler A; Berger M; Schafers M; Heneka MT. 2009. NOS2 gene deficiency protects from sepsis-induced long-term cognitive deficits. J Neurosci 29(45):14177-84. [PubMed: 19906966]  [MGI Ref ID J:154742]

Wei W; Li B; Hanes MA; Kakar S; Chen X; Liu L. 2010. S-nitrosylation from GSNOR deficiency impairs DNA repair and promotes hepatocarcinogenesis. Sci Transl Med 2(19):19ra13. [PubMed: 20371487]  [MGI Ref ID J:167883]

Wei W; Yang Z; Tang CH; Liu L. 2011. Targeted deletion of GSNOR in hepatocytes of mice causes nitrosative inactivation of O6-alkylguanine-DNA alkyltransferase and increased sensitivity to genotoxic diethylnitrosamine. Carcinogenesis 32(7):973-7. [PubMed: 21385828]  [MGI Ref ID J:173666]

White JK; Mastroeni P; Popoff JF; Evans CA; Blackwell JM. 2005. Slc11a1-mediated resistance to Salmonella enterica serovar Typhimurium and Leishmania donovani infections does not require functional inducible nitric oxide synthase or phagocyte oxidase activity. J Leukoc Biol 77(3):311-20. [PubMed: 15601666]  [MGI Ref ID J:97453]

Whiteus C; Freitas C; Grutzendler J. 2014. Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period. Nature 505(7483):407-11. [PubMed: 24305053]  [MGI Ref ID J:207919]

Wiese M; Gerlach RG; Popp I; Matuszak J; Mahapatro M; Castiglione K; Chakravortty D; Willam C; Hensel M; Bogdan C; Jantsch J. 2012. Hypoxia-mediated impairment of the mitochondrial respiratory chain inhibits the bactericidal activity of macrophages. Infect Immun 80(4):1455-66. [PubMed: 22252868]  [MGI Ref ID J:182549]

Wilcock DM; Gharkholonarehe N; Van Nostrand WE; Davis J; Vitek MP; Colton CA. 2009. Amyloid reduction by amyloid-beta vaccination also reduces mouse tau pathology and protects from neuron loss in two mouse models of Alzheimer's disease. J Neurosci 29(25):7957-65. [PubMed: 19553436]  [MGI Ref ID J:150418]

Wilcock DM; Lewis MR; Van Nostrand WE; Davis J; Previti ML; Gharkholonarehe N; Vitek MP; Colton CA. 2008. Progression of amyloid pathology to Alzheimer's disease pathology in an amyloid precursor protein transgenic mouse model by removal of nitric oxide synthase 2. J Neurosci 28(7):1537-45. [PubMed: 18272675]  [MGI Ref ID J:132221]

Wilcock DM; Vitek MP; Colton CA. 2009. Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer's disease. Neuroscience 159(3):1055-69. [PubMed: 19356689]  [MGI Ref ID J:148938]

Winter SE; Winter MG; Xavier MN; Thiennimitr P; Poon V; Keestra AM; Laughlin RC; Gomez G; Wu J; Lawhon SD; Popova IE; Parikh SJ; Adams LG; Tsolis RM; Stewart VJ; Baumler AJ. 2013. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science 339(6120):708-11. [PubMed: 23393266]  [MGI Ref ID J:193601]

Wipke BT; Allen PM. 2001. Essential role of neutrophils in the initiation and progression of a murine model of rheumatoid arthritis. J Immunol 167(3):1601-8. [PubMed: 11466382]  [MGI Ref ID J:120467]

Wood KC; Hebbel RP; Lefer DJ; Granger DN. 2006. Critical role of endothelial cell-derived nitric oxide synthase in sickle cell disease-induced microvascular dysfunction. Free Radic Biol Med 40(8):1443-53. [PubMed: 16631534]  [MGI Ref ID J:108238]

Wu D; Xu C; Cederbaum A. 2009. Role of nitric oxide and nuclear factor-kappaB in the CYP2E1 potentiation of tumor necrosis factor alpha hepatotoxicity in mice. Free Radic Biol Med 46(4):480-91. [PubMed: 19063961]  [MGI Ref ID J:145179]

Wuthrich M; Filutowicz HI; Warner T; Klein BS. 2002. Requisite elements in vaccine immunity to Blastomyces dermatitidis: plasticity uncovers vaccine potential in immune-deficient hosts. J Immunol 169(12):6969-76. [PubMed: 12471131]  [MGI Ref ID J:118419]

Xi L; Jarrett NC; Hess ML; Kukreja RC. 1999. Essential role of inducible nitric oxide synthase in monophosphoryl lipid A-induced late cardioprotection: evidence from pharmacological inhibition and gene knockout mice. Circulation 99(16):2157-63. [PubMed: 10217657]  [MGI Ref ID J:54841]

Xi L; Jarrett NC; Hess ML; Kukreja RC. 1999. Myocardial ischemia/reperfusion injury in the inducible nitric oxide synthase knockout mice. Life Sci 65(9):935-45. [PubMed: 10465353]  [MGI Ref ID J:57432]

Xu G; Zhang Y; Zhang L; Ren G; Shi Y. 2008. Bone marrow stromal cells induce apoptosis of lymphoma cells in the presence of IFNgamma and TNF by producing nitric oxide. Biochem Biophys Res Commun 375(4):666-70. [PubMed: 18755151]  [MGI Ref ID J:140996]

Xu W; Xin L; Soong L; Zhang K. 2011. Sphingolipid degradation by Leishmania major is required for its resistance to acidic pH in the mammalian host. Infect Immun 79(8):3377-87. [PubMed: 21576322]  [MGI Ref ID J:175272]

Yan BS; Pichugin AV; Jobe O; Helming L; Eruslanov EB; Gutierrez-Pabello JA; Rojas M; Shebzukhov YV; Kobzik L; Kramnik I. 2007. Progression of pulmonary tuberculosis and efficiency of bacillus Calmette-Guerin vaccination are genetically controlled via a common sst1-mediated mechanism of innate immunity. J Immunol 179(10):6919-32. [PubMed: 17982083]  [MGI Ref ID J:154010]

Yang JZ; Ajonuma LC; Rowlands DK; Tsang LL; Ho LS; Lam SY; Chen WY; Zhou CX; Chung YW; Cho CY; Tse JY; James AE; Chan HC. 2005. The role of inducible nitric oxide synthase in gamete interaction and fertilization: a comparative study on knockout mice of three NOS isoforms. Cell Biol Int 29(9):785-91. [PubMed: 16087361]  [MGI Ref ID J:112824]

Yang S; Porter VA; Cornfield DN; Milla C; Panoskaltsis-Mortari A; Blazar BR; Haddad IY. 2001. Effects of oxidant stress on inflammation and survival of iNOS knockout mice after marrow transplantation. Am J Physiol Lung Cell Mol Physiol 281(4):L922-30. [PubMed: 11557596]  [MGI Ref ID J:72096]

Yang Z; Wang ZE; Doulias PT; Wei W; Ischiropoulos H; Locksley RM; Liu L. 2010. Lymphocyte Development Requires S-nitrosoglutathione Reductase. J Immunol 185(11):6664-9. [PubMed: 20980633]  [MGI Ref ID J:166150]

Yerushalmi HF; Besselsen DG; Ignatenko NA; Blohm-Mangone KA; Padilla-Torres JL; Stringer DE; Cui H; Holubec H; Payne CM; Gerner EW. 2006. The role of NO synthases in arginine-dependent small intestinal and colonic carcinogenesis. Mol Carcinog 45(2):93-105. [PubMed: 16329147]  [MGI Ref ID J:107079]

Yook YH; Kang KH; Maeng O; Kim TR; Lee JO; Kang KI; Kim YS; Paik SG; Lee H. 2004. Nitric oxide induces BNIP3 expression that causes cell death in macrophages. Biochem Biophys Res Commun 321(2):298-305. [PubMed: 15358175]  [MGI Ref ID J:91305]

Zaki MH; Fujii S; Okamoto T; Islam S; Khan S; Ahmed KA; Sawa T; Akaike T. 2009. Cytoprotective function of heme oxygenase 1 induced by a nitrated cyclic nucleotide formed during murine salmonellosis. J Immunol 182(6):3746-56. [PubMed: 19265153]  [MGI Ref ID J:145919]

Zaragoza C; Lopez-Rivera E; Garcia-Rama C; Saura M; Martinez-Ruiz A; Lizarbe TR; Martin-de-Lara F; Lamas S. 2006. Cbfa-1 mediates nitric oxide regulation of MMP-13 in osteoblasts. J Cell Sci 119(Pt 9):1896-902. [PubMed: 16636074]  [MGI Ref ID J:108930]

Zaragoza C; Ocampo CJ; Saura M; Bao C; Leppo M; Lafond-Walker A; Thiemann DR; Hruban R; Lowenstein CJ. 1999. Inducible nitric oxide synthase protection against coxsackievirus pancreatitis. J Immunol 163(10):5497-504. [PubMed: 10553076]  [MGI Ref ID J:58451]

Zeidler PC; Millecchia LM; Castranova V. 2004. Role of inducible nitric oxide synthase-derived nitric oxide in lipopolysaccharide plus interferon-gamma-induced pulmonary inflammation. Toxicol Appl Pharmacol 195(1):45-54. [PubMed: 14962504]  [MGI Ref ID J:87978]

Zelickson BR; Benavides GA; Johnson MS; Chacko BK; Venkatraman A; Landar A; Betancourt AM; Bailey SM; Darley-Usmar VM. 2011. Nitric oxide and hypoxia exacerbate alcohol-induced mitochondrial dysfunction in hepatocytes. Biochim Biophys Acta 1807(12):1573-82. [PubMed: 21971515]  [MGI Ref ID J:180333]

Zell JA; Ignatenko NA; Yerushalmi HF; Ziogas A; Besselsen DG; Gerner EW; Anton-Culver H. 2007. Risk and risk reduction involving arginine intake and meat consumption in colorectal tumorigenesis and survival. Int J Cancer 120(3):459-68. [PubMed: 17096347]  [MGI Ref ID J:117825]

Zhang P; Xu X; Hu X; van Deel ED; Zhu G; Chen Y. 2007. Inducible nitric oxide synthase deficiency protects the heart from systolic overload-induced ventricular hypertrophy and congestive heart failure. Circ Res 100(7):1089-98. [PubMed: 17363700]  [MGI Ref ID J:133913]

Zhao T; Xi L; Chelliah J; Levasseur JE; Kukreja RC. 2000. Inducible nitric oxide synthase mediates delayed myocardial protection induced by activation of adenosine A(1) receptors: evidence from gene-knockout mice. Circulation 102(8):902-7. [PubMed: 10952960]  [MGI Ref ID J:103302]

Zhao TC; Zhang L; Liu JT; Guo TL. 2012. Disruption of Nox2 and TNFRp55/p75 eliminates cardioprotection induced by anisomycin. Am J Physiol Heart Circ Physiol 303(10):H1263-72. [PubMed: 22982779]  [MGI Ref ID J:191277]

Zhao Y; Ferguson DJ; Wilson DC; Howard JC; Sibley LD; Yap GS. 2009. Virulent Toxoplasma gondii evade immunity-related GTPase-mediated parasite vacuole disruption within primed macrophages. J Immunol 182(6):3775-81. [PubMed: 19265156]  [MGI Ref ID J:145916]

Zhou J; Dehne N; Brune B. 2009. Nitric oxide causes macrophage migration via the HIF-1-stimulated small GTPases Cdc42 and Rac1. Free Radic Biol Med 47(6):741-9. [PubMed: 19523512]  [MGI Ref ID J:152571]

Zhou J; Tang PC; Qin L; Gayed PM; Li W; Skokos EA; Kyriakides TR; Pober JS; Tellides G. 2010. CXCR3-dependent accumulation and activation of perivascular macrophages is necessary for homeostatic arterial remodeling to hemodynamic stresses. J Exp Med 207(9):1951-66. [PubMed: 20733031]  [MGI Ref ID J:165720]

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Zhu X; Zhao H; Graveline AR; Buys ES; Schmidt U; Bloch KD; Rosenzweig A; Chao W. 2006. MyD88 and NOS2 are essential for toll-like receptor 4-mediated survival effect in cardiomyocytes. Am J Physiol Heart Circ Physiol 291(4):H1900-9. [PubMed: 16648192]  [MGI Ref ID J:116319]

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Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice may be bred as homozygotes. Colony managers at The Jackson Laboratory report these mice have a tendency to aggressively barber one another (specifically the whiskers). Attempts to breed away from this characteristic have not been successful to date (June 2009).
Mating SystemHomozygote x Homozygote         (Female x Male)   01-MAR-06
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $239.00Female or MaleHomozygous for Nos2tm1Lau  
Price per Pair (US dollars $)Pair Genotype
$478.00Homozygous for Nos2tm1Lau x Homozygous for Nos2tm1Lau  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $310.70Female or MaleHomozygous for Nos2tm1Lau  
Price per Pair (US dollars $)Pair Genotype
$621.40Homozygous for Nos2tm1Lau x Homozygous for Nos2tm1Lau  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   100903 B6129PF2/J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

Important Note

Of note, colony managers at The Jackson Laboratory report these mice have a tendency to aggressively barber one another (specifically the whiskers). Attempts to breed away from this characteristic have not been successful to date (June 2009).

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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JAX® Mice
Surgical and Preconditioning Services
JAX® Services
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Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
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Terms of Use

Terms of Use


General Terms and Conditions


Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


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