Strain Name:

B6.129P2-Nos2tm1Lau/J

Stock Number:

002609

Availability:

Level 3

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered Mutant Mice.
Mating SystemHomozygote x Homozygote         (Female x Male)
Specieslaboratory mouse
Background Strain C57BL/6
Donor Strain 129P2 via E14TG2a ES cell line
GenerationN11F10 (20-DEC-06)
 
Donating Investigator Victor Laubach,   University of Virginia Health Sci. Ctr.

Appearance
black
Related Genotype: a/a

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.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 12 and 13, encoding the calmodulin binding domain. The construct was electroporated into 129P2/OlaHsd derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6J for 11 generations.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Nos2tm1Lau allele
004684   B6(129P2) Nos2tm1Lau-chtl/J
002596   B6;129P2-Nos2tm1Lau/J
View Strains carrying   Nos2tm1Lau     (2 strains)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Nos2tm1Lau/Nos2tm1Lau

        B6.129P2-Nos2tm1Lau
  • cardiovascular system phenotype
  • abnormal blood pressure (MGI Ref ID J:115413)
    • 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
    • decreased systolic blood pressure (MGI Ref ID J:104749)
      • more significant drop in systolic blood pressure after myocardial infarction than is seen in controls
  • abnormal heart morphology (MGI Ref ID J:108269)
    • abnormal cardiac muscle morphology (MGI Ref ID J:71505)
      • increased hyalination and patchy loss of cross-striations when on 100% oxygen
    • abnormal heart ventricle morphology (MGI Ref ID J:108269)
      • hypoxia causes less increase in the RV/LV+Septum ratio than is found in controls
  • abnormal physiological neovascularization (MGI Ref ID J:106207)
    • retinae show much less neovascularization and significantly less lesions 14 days after production of photocoagulation burns compared to heterozygous littermates
    • retinal revascularization after ischemia produces small highly branched blood vessels
    • three fold more branching occurs in revascularization than occurs in controls
  • choroidal neovascularization (MGI Ref ID J:106207)
    • knockouts show a significant decrease in the amount of neovascularization compared to heterozygous littermates
  • vision/eye phenotype
  • choroidal neovascularization (MGI Ref ID J:106207)
    • knockouts show a significant decrease in the amount of neovascularization compared to heterozygous littermates
  • nervous system phenotype
  • abnormal central nervous system regeneration (MGI Ref ID J:110081)
    • recover better from compression injury to the spinal cord than do controls, severity of behavioral deficit due to injury is somewhat less
  • abnormal corpus callosum morphology (MGI Ref ID J:125459)
    • increased myelin pathology after treatment with cuprizone
  • abnormal oligodendrocyte morphology (MGI Ref ID J:125459)
    • decreased numbers of mature oligodendrocytes after cuprizone treatment
    • numbers of oligodendrocytes reduced to 50% of controls after 3.5 weeks
    • undergo increased apoptosis which is not seen for microglia and astrocytes
  • increased susceptibility to pharmacologically induced seizures (MGI Ref ID J:107300)
    • shortened latency to seizures induced by kainic acid when on a normal diet
    • behavior responses correspond to grade V seizures
    • latency to seizure is prolonged when fed a ketogenic diet
  • digestive/alimentary phenotype
  • decreased susceptibility to induced colitis (MGI Ref ID J:87601)
    • less susceptibility to dextran sodium sulfate induced colitis
    • less severe weight loss, blood loss and macroscopic damage
    • improved survival
  • homeostasis/metabolism phenotype
  • abnormal blood coagulation (MGI Ref ID J:117987)
    • shorter time to thrombus formation and vessel occlusion
    • abnormal platelet physiology (MGI Ref ID J:117987)
      • increased platelet deposition
  • abnormal glucose homeostasis (MGI Ref ID J:95957)
    • no effect on streptozotocin induced diabetis
  • enhanced wound healing (MGI Ref ID J:110081)
    • recover better from compression injury to the spinal cord than do controls, severity of behavioral deficit due to injury is somewhat less
  • increased susceptibility to pharmacologically induced seizures (MGI Ref ID J:107300)
    • shortened latency to seizures induced by kainic acid when on a normal diet
    • behavior responses correspond to grade V seizures
    • latency to seizure is prolonged when fed a ketogenic diet
  • behavior/neurological phenotype
  • abnormal frequency of paradoxical sleep (MGI Ref ID J:83571)
    • significantly more time spent in REM sleep during the light period
    • increased REM sleep results from more REM episodes and shortened periods in between
    • more non REM sleep episodes in light period but of shorter duration
    • significantly less non REM sleep during dark periods
  • decreased eating behavior (MGI Ref ID J:112153)
    • inhibitory effect of insulin on feeding is enhanced by 10 -8M TNF alpha
  • increased susceptibility to pharmacologically induced seizures (MGI Ref ID J:107300)
    • shortened latency to seizures induced by kainic acid when on a normal diet
    • behavior responses correspond to grade V seizures
    • latency to seizure is prolonged when fed a ketogenic diet
  • respiratory system phenotype
  • *normal* respiratory system phenotype (MGI Ref ID J:71505)
    • alveolar fluid clearance unaffected by amilorid and forskolin which both affect clearance in controls
    • abnormal respiratory bronchiole morphology (MGI Ref ID J:71505)
      • increased ulceration in 100% oxygen than seen with controls
    • abnormal respiratory system physiology (MGI Ref ID J:71505)
      • reduced lung injury relative to controls after 55 hours at 100% oxygen
  • life span-post-weaning/aging
  • *normal* life span-post-weaning/aging (MGI Ref ID J:115413)
    • better survival after myocardial infarction than for wild-type controls
    • increased mortality induced by ionizing radiation (MGI Ref ID J:98135)
      • increased sensitivity to ionizing radiation
  • immune system phenotype
  • abnormal osteoclast morphology (MGI Ref ID J:112399)
    • elevated osteoclast surface to bone surface in comparison to controls 7 days after bone reloading
  • decreased susceptibility to induced colitis (MGI Ref ID J:87601)
    • less susceptibility to dextran sodium sulfate induced colitis
    • less severe weight loss, blood loss and macroscopic damage
    • improved survival
  • hematopoietic system phenotype
  • abnormal osteoclast morphology (MGI Ref ID J:112399)
    • elevated osteoclast surface to bone surface in comparison to controls 7 days after bone reloading
  • abnormal platelet physiology (MGI Ref ID J:117987)
    • increased platelet deposition
  • cellular phenotype
  • abnormal apoptosis (MGI Ref ID J:115413)
    • frequency of apoptosis is less than in control mice but higher than sham operated animals 4 months after myocardial infarction
  • skeleton phenotype
  • abnormal bone mineralization (MGI Ref ID J:112399)
    • lower mineral aposition rate than in controls 7 days after bone reloading
  • abnormal bone structure (MGI Ref ID J:112399)
    • less recovery of lost bone volume due to bone unloading 7 days after reloading
    • abnormal osteoclast morphology (MGI Ref ID J:112399)
      • elevated osteoclast surface to bone surface in comparison to controls 7 days after bone reloading
  • muscle phenotype
  • abnormal cardiac muscle morphology (MGI Ref ID J:71505)
    • increased hyalination and patchy loss of cross-striations when on 100% oxygen

Nos2tm1Lau/Nos2tm1Lau

        B6.129P2-Nos2tm1Lau/J
  • respiratory system phenotype
  • abnormal surfactant physiology (MGI Ref ID J:130520)
    • 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
    • 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

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Nos2tm1Lau/Nos2tm1Lau

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

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

Internal/Organ Research
Wound Healing (delayed/impaired)

Neurobiology Research
Parkinson's Disease (resistance to MPTP)

Nos2tm1Lau related

Immunology and Inflammation Research
Inflammation (Inflammatory bowel disease)

Genes & Alleles

Gene & Allele Information

Allele Symbol Nos2tm1Lau
Allele Name targeted mutation 1, Victor E Laubach
Allele Type Targeted (knock-out)
Common Name(s) NOS2-; NOS2tm/Lau; Nos2tm1Lau; iNOS-;
Mutation Made By 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:29677]

Genotyping

Genotyping Information

Genotyping Protocols

Nos2tm1Lau, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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

Alcaide P; Fresno M. 2004. The Trypanosoma cruzi membrane mucin AgC10 inhibits T cell activation and IL-2 transcription through L-selectin. Int Immunol 16(10):1365-75. [PubMed: 15314038]  [MGI Ref ID J:93640]

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]

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]

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]

Ellies LG; Fishman M; Hardison J; Kleeman J; Maglione JE; Manner CK; Cardiff RD; MacLeod CL. 2003. Mammary tumor latency is increased in mice lacking the inducible nitric oxide synthase. Int J Cancer 106(1):1-7. [PubMed: 12794750]  [MGI Ref ID J:84004]

Falcone S; Perrotta C; De Palma C; Pisconti A; Sciorati C; Capobianco A; Rovere-Querini P; Manfredi AA; Clementi E. 2004. Activation of acid sphingomyelinase and its inhibition by the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway: key events in Escherichia coli-elicited apoptosis of dendritic cells. J Immunol 173(7):4452-63. [PubMed: 15383576]  [MGI Ref ID J:93735]

Gobert AP; Cheng Y; Akhtar M; Mersey BD; Blumberg DR; Cross RK; Chaturvedi R; Drachenberg CB; Boucher JL; Hacker A; Casero RA Jr; Wilson KT. 2004. Protective role of arginase in a mouse model of colitis. J Immunol 173(3):2109-17. [PubMed: 15265947]  [MGI Ref ID J:92035]

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]

Hardiman KM; Lindsey JR; Matalon S. 2001. Lack of amiloride-sensitive transport across alveolar and respiratory epithelium of iNOS(-/-) mice in vivo. Am J Physiol Lung Cell Mol Physiol 281(3):L722-31. [PubMed: 11504701]  [MGI Ref ID J:71505]

Hayashi T; Rao SP; Takabayashi K; Van Uden JH; Kornbluth RS; Baird SM; Taylor MW; Carson DA; Catanzaro A; Raz E. 2001. Enhancement of Innate Immunity against Mycobacterium avium Infection by Immunostimulatory DNA Is Mediated by Indoleamine 2,3-Dioxygenase. Infect Immun 69(10):6156-64. [PubMed: 11553555]  [MGI Ref ID J:71646]

Ko J; Gendron-Fitzpatrick A; Splitter GA. 2002. Susceptibility of IFN regulatory factor-1 and IFN consensus sequence binding protein-deficient mice to brucellosis. J Immunol 168(5):2433-40. [PubMed: 11859135]  [MGI Ref ID J:74725]

Mattner J; Wandersee-Steinhauser A; Pahl A; Rollinghoff M; Majeau GR; Hochman PS; Bogdan C. 2004. Protection against progressive leishmaniasis by IFN-beta. J Immunol 172(12):7574-82. [PubMed: 15187137]  [MGI Ref ID J:90823]

McKim SE; Gabele E; Isayama F; Lambert JC; Tucker LM; Wheeler MD; Connor HD; Mason RP; Doll MA; Hein DW; Arteel GE. 2003. Inducible nitric oxide synthase is required in alcohol-induced liver injury: studies with knockout mice. Gastroenterology 125(6):1834-44. [PubMed: 14724835]  [MGI Ref ID J:86852]

Miller BH; Fratti RA; Poschet JF; Timmins GS; Master SS; Burgos M; Marletta MA; Deretic V. 2004. Mycobacteria inhibit nitric oxide synthase recruitment to phagosomes during macrophage infection. Infect Immun 72(5):2872-8. [PubMed: 15102799]  [MGI Ref ID J:89478]

Perreault M; Marette A. 2001. Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle. Nat Med 7(10):1138-43. [PubMed: 11590438]  [MGI Ref ID J:72215]

Tranguch S; Huet-Hudson Y. 2003. Decreased viability of nitric oxide synthase double knockout mice. Mol Reprod Dev 65(2):175-9. [PubMed: 12704728]  [MGI Ref ID J:83112]

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]

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]

de Jonge WJ; Hallemeesch MM; Kwikkers KL; Ruijter JM; de Gier-de Vries C; van Roon MA; Meijer AJ; Marescau B; de Deyn PP; Deutz NE; Lamers WH. 2002. Overexpression of arginase I in enterocytes of transgenic mice elicits a selective arginine deficiency and affects skin, muscle, and lymphoid development. Am J Clin Nutr 76(1):128-40. [PubMed: 12081826]  [MGI Ref ID J:80556]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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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]

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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]

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Davie SA; Maglione JE; Manner CK; Young D; Cardiff RD; MacLeod CL; Ellies LG. 2007. Effects of FVB/NJ and C57Bl/6J strain backgrounds on mammary tumor phenotype in inducible nitric oxide synthase deficient mice. Transgenic Res 16(2):193-201. [PubMed: 17206489]  [MGI Ref ID J:121391]

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Gobert AP; Cheng Y; Akhtar M; Mersey BD; Blumberg DR; Cross RK; Chaturvedi R; Drachenberg CB; Boucher JL; Hacker A; Casero RA Jr; Wilson KT. 2004. Protective role of arginase in a mouse model of colitis. J Immunol 173(3):2109-17. [PubMed: 15265947]  [MGI Ref ID J:92035]

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Gonzalez C; Cuvellier S; Hue-Beauvais C; Levi-Strauss M. 2003. Genetic control of non obese diabetic mice susceptibility to high-dose streptozotocin-induced diabetes. Diabetologia 46(9):1291-5. [PubMed: 12879252]  [MGI Ref ID J:95957]

Gramaglia I; Sobolewski P; Meays D; Contreras R; Nolan JP; Frangos JA; Intaglietta M; van der Heyde HC. 2006. Low nitric oxide bioavailability contributes to the genesis of experimental cerebral malaria. Nat Med 12(12):1417-22. [PubMed: 17099710]  [MGI Ref ID J:129543]

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Guhring H; Gorig M; Ates M; Coste O; Zeilhofer HU; Pahl A; Rehse K; Brune K. 2000. Suppressed injury-induced rise in spinal prostaglandin E2 production and reduced early thermal hyperalgesia in iNOS-deficient mice. J Neurosci 20(17):6714-20. [PubMed: 10964977]  [MGI Ref ID J:64215]

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]

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Hampton TG; Amende I; Fong J; Laubach VE; Li J; Metais C; Simons M. 2000. Basic FGF reduces stunning via a NOS2-dependent pathway in coronary-perfused mouse hearts. Am J Physiol Heart Circ Physiol 279(1):H260-8. [PubMed: 10899065]  [MGI Ref ID J:107850]

Hardiman KM; Lindsey JR; Matalon S. 2001. Lack of amiloride-sensitive transport across alveolar and respiratory epithelium of iNOS(-/-) mice in vivo. Am J Physiol Lung Cell Mol Physiol 281(3):L722-31. [PubMed: 11504701]  [MGI Ref ID J:71505]

Hegazi RA; Rao KN; Mayle A; Sepulveda AR; Otterbein LE; Plevy SE. 2005. Carbon monoxide ameliorates chronic murine colitis through a heme oxygenase 1-dependent pathway. J Exp Med 202(12):1703-13. [PubMed: 16365149]  [MGI Ref ID J:118826]

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Hickman-Davis JM; Wang Z; Fierro-Perez GA; Chess PR; Page GP; Matalon S; Notter RH. 2007. Surfactant dysfunction in SP-A-/- and iNOS-/- mice with mycoplasma infection. Am J Respir Cell Mol Biol 36(1):103-13. [PubMed: 16917077]  [MGI Ref ID J:130520]

Hokari R; Kato S; Matsuzaki K; Kuroki M; Iwai A; Kawaguchi A; Nagao S; Miyahara T; Itoh K; Sekizuka E; Nagata H; Ishii H; Miura S. 2001. Reduced sensitivity of inducible nitric oxide synthase-deficient mice to chronic colitis. Free Radic Biol Med 31(2):153-63. [PubMed: 11440827]  [MGI Ref ID J:70811]

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Houpt ER; Glembocki DJ; Obrig TG; Moskaluk CA; Lockhart LA; Wright RL; Seaner RM; Keepers TR; Wilkins TD; Petri WA Jr. 2002. The mouse model of amebic colitis reveals mouse strain susceptibility to infection and exacerbation of disease by CD4+ T cells. J Immunol 169(8):4496-503. [PubMed: 12370386]  [MGI Ref ID J:120012]

Hromatka BS; Noble SM; Johnson AD. 2005. Transcriptional response of Candida albicans to nitric oxide and the role of the YHB1 gene in nitrosative stress and virulence. Mol Biol Cell 16(10):4814-26. [PubMed: 16030247]  [MGI Ref ID J:106530]

Huang B; Pan PY; Li Q; Sato AI; Levy DE; Bromberg J; Divino CM; Chen SH. 2006. Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res 66(2):1123-31. [PubMed: 16424049]  [MGI Ref ID J:106544]

Hussain MB; Hobbs AJ; MacAllister RJ. 1999. Autoregulation of nitric oxide-soluble guanylate cyclase-cyclic GMP signalling in mouse thoracic aorta. Br J Pharmacol 128(5):1082-8. [PubMed: 10556946]  [MGI Ref ID J:59681]

Hussain SP; He P; Subleski J; Hofseth LJ; Trivers GE; Mechanic L; Hofseth AB; Bernard M; Schwank J; Nguyen G; Mathe E; Djurickovic D; Haines D; Weiss J; Back T; Gruys E; Laubach VE; Wiltrout RH; Harris CC. 2008. Nitric oxide is a key component in inflammation-accelerated tumorigenesis. Cancer Res 68(17):7130-6. [PubMed: 18757428]  [MGI Ref ID J:138926]

Hussain SP; Trivers GE; Hofseth LJ; He P; Shaikh I; Mechanic LE; Doja S; Jiang W; Subleski J; Shorts L; Haines D; Laubach VE; Wiltrout RH; Djurickovic D; Harris CC. 2004. Nitric oxide, a mediator of inflammation, suppresses tumorigenesis. Cancer Res 64(19):6849-53. [PubMed: 15466171]  [MGI Ref ID J:93662]

Hutchinson D; Ho V; Dodd M; Dawson HN; Zumwalt AC; Schmitt D; Colton CA. 2007. Quantitative measurement of postural sway in mouse models of human neurodegenerative disease. Neuroscience 148(4):825-32. [PubMed: 17764851]  [MGI Ref ID J:128390]

Ii M; Nishimura H; Iwakura A; Wecker A; Eaton E; Asahara T; Losordo DW. 2005. Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via 'imported' nitric oxide synthase activity. Circulation 111(9):1114-20. [PubMed: 15723985]  [MGI Ref ID J:108997]

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Isaksson J; Farooque M; Olsson Y. 2005. Improved functional outcome after spinal cord injury in iNOS-deficient mice. Spinal Cord 43(3):167-70. [PubMed: 15520837]  [MGI Ref ID J:110081]

Itzhak Y; Martin JL; Ali SF. 1999. Methamphetamine- and 1-methyl-4-phenyl- 1,2,3, 6-tetrahydropyridine-induced dopaminergic neurotoxicity in inducible nitric oxide synthase-deficient mice. Synapse 34(4):305-12. [PubMed: 10529724]  [MGI Ref ID J:59707]

Iwakiri Y; Cadelina G; Sessa WC; Groszmann RJ. 2002. Mice with targeted deletion of eNOS develop hyperdynamic circulation associated with portal hypertension. Am J Physiol Gastrointest Liver Physiol 283(5):G1074-81. [PubMed: 12381520]  [MGI Ref ID J:108056]

Jones SP; Greer JJ; Ware PD; Yang J; Walsh K; Lefer DJ. 2005. Deficiency of iNOS does not attenuate severe congestive heart failure in mice. Am J Physiol Heart Circ Physiol 288(1):H365-70. [PubMed: 15319210]  [MGI Ref ID J:95577]

Jones SP; Trocha SD; Lefer DJ. 2001. Cardioprotective actions of endogenous IL-10 are independent of iNOS. Am J Physiol Heart Circ Physiol 281(1):H48-52. [PubMed: 11406467]  [MGI Ref ID J:70292]

Joo JD; Kim M; Horst P; Kim J; D'Agati VD; Emala CW Sr; Lee HT. 2007. Acute and delayed renal protection against renal ischemia and reperfusion injury with A1 adenosine receptors. Am J Physiol Renal Physiol 293(6):F1847-57. [PubMed: 17928414]  [MGI Ref ID J:127544]

Kahl KG; Schmidt HH; Jung S; Sherman P; Toyka KV; Zielasek J. 2004. Experimental autoimmune encephalomyelitis in mice with a targeted deletion of the inducible nitric oxide synthase gene: increased T-helper 1 response. Neurosci Lett 358(1):58-62. [PubMed: 15016434]  [MGI Ref ID J:88809]

Kalns J; Scruggs J; Millenbaugh N; Vivekananda J; Shealy D; Eggers J; Kiel J. 2002. TNF Receptor 1, IL-1 Receptor, and iNOS Genetic Knockout Mice Are Not Protected from Anthrax Infection. Biochem Biophys Res Commun 292(1):41-4. [PubMed: 11890668]  [MGI Ref ID J:75694]

Kenyon NJ; van der Vliet A; Schock BC; Okamoto T; McGrew GM; Last JA. 2002. Susceptibility to ozone-induced acute lung injury in iNOS-deficient mice. Am J Physiol Lung Cell Mol Physiol 282(3):L540-5. [PubMed: 11839550]  [MGI Ref ID J:75613]

Kim HA; Kim SH; Ko HM; Choi JH; Kim KJ; Oh SH; Cho KO; Choi IW; Im SY. 2008. Nitric oxide plays a key role in the platelet-activating factor-induced enhancement of resistance against systemic candidiasis. Immunology 124(3):428-35. [PubMed: 18397269]  [MGI Ref ID J:138455]

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]

Kitayama J; Faraci FM; Gunnett CA; Heistad DD. 2006. Impairment of dilator responses of cerebral arterioles during diabetes mellitus: role of inducible NO synthase. Stroke 37(8):2129-33. [PubMed: 16809563]  [MGI Ref ID J:135707]

Kleeberger SR; Reddy SP; Zhang LY; Cho HY; Jedlicka AE. 2001. Toll-like receptor 4 mediates ozone-induced murine lung hyperpermeability via inducible nitric oxide synthase. Am J Physiol Lung Cell Mol Physiol 280(2):L326-33. [PubMed: 11159012]  [MGI Ref ID J:108671]

Klingstrom J; Akerstrom S; Hardestam J; Stoltz M; Simon M; Falk KI; Mirazimi A; Rottenberg M; Lundkvist A. 2006. Nitric oxide and peroxynitrite have different antiviral effects against hantavirus replication and free mature virions. Eur J Immunol 36(10):2649-57. [PubMed: 16955520]  [MGI Ref ID J:118085]

Knotek M; Rogachev B; Wang W; Ecder T; Melnikov V; Gengaro PE; Esson M; Edelstein CL; Dinarello CA; Schrier RW. 2001. Endotoxemic renal failure in mice: Role of tumor necrosis factor independent of inducible nitric oxide synthase. Kidney Int 59(6):2243-9. [PubMed: 11380827]  [MGI Ref ID J:104003]

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Kotamraju S; Matalon S; Matsunaga T; Shang T; Hickman-Davis JM; Kalyanaraman B. 2006. Upregulation of immunoproteasomes by nitric oxide: Potential antioxidative mechanism in endothelial cells. Free Radic Biol Med 40(6):1034-44. [PubMed: 16540399]  [MGI Ref ID J:107075]

Kozak W; Kozak A. 2003. Genetic Models in Applied Physiology. Differential role of nitric oxide synthase isoforms in fever of different etiologies: studies using Nos gene-deficient mice. J Appl Physiol 94(6):2534-44. [PubMed: 12562678]  [MGI Ref ID J:103018]

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Krieglstein CF; Cerwinka WH; Laroux FS; Salter JW; Russell JM; Schuermann G; Grisham MB; Ross CR; Granger DN. 2001. Regulation of murine intestinal inflammation by reactive metabolites of oxygen and nitrogen: divergent roles of superoxide and nitric oxide. J Exp Med 194(9):1207-18. [PubMed: 11696587]  [MGI Ref ID J:134388]

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Kurtz S; McKinnon KP; Runge MS; Ting JP; Braunstein M. 2006. The SecA2 secretion factor of Mycobacterium tuberculosis promotes growth in macrophages and inhibits the host immune response. Infect Immun 74(12):6855-64. [PubMed: 17030572]  [MGI Ref ID J:116072]

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Leal EC; Manivannan A; Hosoya K; Terasaki T; Cunha-Vaz J; Ambrosio AF; Forrester JV. 2007. Inducible nitric oxide synthase isoform is a key mediator of leukostasis and blood-retinal barrier breakdown in diabetic retinopathy. Invest Ophthalmol Vis Sci 48(11):5257-65. [PubMed: 17962481]  [MGI Ref ID J:127155]

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Li D; Laubach VE; Johns RA. 2001. Upregulation of lung soluble guanylate cyclase during chronic hypoxia is prevented by deletion of eNOS. Am J Physiol Lung Cell Mol Physiol 281(2):L369-76. [PubMed: 11435211]  [MGI Ref ID J:108269]

Li E; Zhou P; Singer SM. 2006. Neuronal nitric oxide synthase is necessary for elimination of Giardia lamblia infections in mice. J Immunol 176(1):516-21. [PubMed: 16365445]  [MGI Ref ID J:126256]

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Libby RT; Howell GR; Pang IH; Savinova OV; Mehalow AK; Barter JW; Smith RS; Clark AF; John SW. 2007. Inducible nitric oxide synthase, Nos2, does not mediate optic neuropathy and retinopathy in the DBA/2J glaucoma model. BMC Neurosci 8:108. [PubMed: 18093296]  [MGI Ref ID J:130816]

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