Strain Name:

B6.129S1-Notch2tm1Grid/J

Stock Number:

010620

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Availability:

Cryopreserved - Ready for recovery

This Notch2del1 hypomorphic mutant mouse strain may be useful in studies of kidney, eye, heart and vascular development.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
GenerationN10p+F5pN1
Generation Definitions
 
Donating Investigator Tom Gridley,   Maine Medical Center Research Institute

Description
Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Due to alternative splicing, 2 in-frame gene products (mRNA) are detected by RT-PCR analysis of homozygous embryos. The mutant transcripts would produce proteins with one or two EGF repeats deleted. Levels of the mutant transcripts are similar to the wildtype transcript level. This targeted allele is a hypomorph. Homozygotes are neonatal lethal due to developmental defects in the kidney, heart and eye vasculature. Homozygous neonates exhibit hypoplastic kidneys, with vasculature lesions at the cortical surface, and lack mature glomeruli. Bilateral microphthalmia, with retrolenticular hyperplasia, is observed in homozygotes. At age embryonic day 11.5, some homozygous embryos exhibit delayed growth, pericardial effusion and widespread hemorrhaging. Homozygous embryos that survive past embryonic day 11.5 display myocardial hypoplasia, hemorrhaging and edema. By embryonic day 13.5, edema and hemorrhaging skin vessels is observed in homozygous embryos.

Development
A targeting vector containing PGK-neo and HSV-tk cassettes was used to delete 0.4 kb of sequence, including most of the exon encoding the EGF repeat 14, the splice donor site, and 0.3 kb of intron sequence. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were crossed to C57BL/6J females and then backcrossed to C57BL/6J for 9 genertions. The mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the distribution colony.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Facebase: models
007664   129S-Efnb1tm1Sor/J
000646   A/J
000647   A/WySnJ
005709   B6.129-Skitm1Cco/J
002619   B6.129-Tgfb3tm1Doe/J
007453   B6.129P2(Cg)-Dhcr7tm1Gst/J
010525   B6.129S-Notch2tm3Grid/J
010616   B6.129S1-Jag1tm1Grid/J
010546   B6.129S1-Jag2tm1Grid/J
009387   B6.129S1-Osr1tm1Jian/J
009386   B6.129S1-Osr2tm1Jian/J
010621   B6.129S1-Snai1tm2.1Grid/J
010617   B6.129S1-Snai2tm1Grid/J
003865   B6.129S2-Itgavtm1Hyn/J
003755   B6.129S4-Meox2tm1(cre)Sor/J
016902   B6.129S5-Irf6Gt(OST398253)Lex/J
003336   B6.129S7-Cdkn1ctm1Sje/J
012843   B6.129X1(Cg)-Slc32a1tm1.1Bgc/J
000026   B6.C3-Gli3Xt-J/J
004275   B6.Cg-Fignfi/Frk
012844   B6.Cg-Gad1tm1.1Bgc/J
006382   B6;129-Casktm1Sud/J
002711   B6;129-Gabrb3tm1Geh/J
004293   B6;129-Shhtm2Amc/J
012603   B6;129-Tgfbr2tm1Karl/J
010618   B6;129S-Jag1tm2Grid/J
010686   B6;129S-Snai1tm2Grid/J
009389   B6;129S1-Bambitm1Jian/J
010619   B6;129S1-Lfngtm1Grid/J
010547   B6;129S1-Notch3tm1Grid/J
010544   B6;129S1-Notch4tm1Grid/J
010722   B6;129S1-Snai2tm2Grid/J
012463   B6;129S4-Foxd1tm1(GFP/cre)Amc/J
022358   B6;129S6-Rr23tm1Axvi/Mmjax
022359   B6;129S6-Rr24tm1Axvi/Mmjax
022360   B6;129S6-Rr25tm1Axvi/Mmjax
003277   B6;129S7-Acvr2atm1Zuk/J
002788   B6;129S7-Fsttm1Zuk/J
002990   B6;129S7-Inhbatm1Zuk/J
000523   B6By.Cg-Eh/J
000278   B6C3Fe a/a-Papss2bm Hps1ep Hps6ru/J
000515   B6CBACa Aw-J/A-SfnEr/J
001434   C3HeB/FeJ x STX/Le-Mc1rE-so Gli3Xt-J Zeb1Tw/J
000252   DC/LeJ
005057   FVB.129-Kcnj2tm1Swz/J
012655   FVB.A-Irf6clft1/BeiJ
013100   FVB.C-Prdm16csp1/J
017437   FVB/N-Ckap5TgTn(sb-cHS4,Tyr)2320F-1Ove/J
017438   FVB/N-MidnTg(Tyr)2261EOve/J
017609   FVB/N-Rr16Tn(sb-Tyr)1HCebOve/J
017598   FVB/N-Sdccag8Tn(sb-Tyr)2161B.CA1C2Ove/J
017608   FVB/N-Skor2Tn(sb-Tyr)1799B.CA7BOve/J
017436   FVB/N-Tapt1TgTn(sb-cHS4,Tyr)2508GOve/J
016870   FVB/NJ-Ap2b1Tg(Tyr)427Ove/EtevJ
017434   FVB;B6-Cramp1lTgTn(sb-rtTA,Tyr)2447AOve/J
017594   FVB;B6-Eya4TgTn(Prm1-sb10,sb-Tyr)1739AOve/J
017435   FVB;B6-SlmapTn(sb-rtTA)2426B.SB4Ove/J
003318   STOCK Shhtm1Amc/J
003102   STOCK Tgfb2tm1Doe/J
018624   STOCK Tgfb3tm2(Tgfb1)Vk/J
008469   STOCK Wnt9btm1.2Amc/J
View Facebase: models     (61 strains)

Strains carrying other alleles of Notch2
010525   B6.129S-Notch2tm3Grid/J
View Strains carrying other alleles of Notch2     (1 strain)

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.
Alagille Syndrome 2; ALGS2   (NOTCH2)
Hajdu-Cheney Syndrome; HJCYS   (NOTCH2)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Notch2tm1Grid/Notch2tm1Grid

        involves: 129S1/Sv * C57BL/6J
  • mortality/aging
  • partial neonatal lethality
    • incomplete penetrance; many animals die within the first 24 hours after birth   (MGI Ref ID J:67157)
  • partial prenatal lethality
    • incomplete penetrance; many embryos die between E12.5-E15.5 and become necrotic   (MGI Ref ID J:67157)
    • at stages after E16.5, only 12% of the embryos are homozygous mutants   (MGI Ref ID J:67157)
  • renal/urinary system phenotype
  • abnormal kidney cortex morphology
    • vascular lesions evident at the cortical surface   (MGI Ref ID J:67157)
    • abnormal podocyte morphology
      • cells that expressed markers of podocyte differentiation were clumped together in the center of the glomerulus, and did not form the cup-shaped epithelial layer observed in the controls   (MGI Ref ID J:67157)
    • abnormal renal glomerulus morphology
      • at E16.5, no morphologically normal glomeruli present   (MGI Ref ID J:67157)
      • frequently, the glomerulus appears as a disorganized clump of cells   (MGI Ref ID J:67157)
      • the glomerular capillary tuft sometimes appears as a capillary aneurysm-like structure that releases red blood cells into the Bowman's capsule   (MGI Ref ID J:67157)
      • abnormal glomerular capillary endothelium morphology
        • few endothelial cells were present in the abnormal mutant glomeruli   (MGI Ref ID J:67157)
      • absent mesangial cell
        • absence of cells that express markers of mesangial cell differentiation in the abnormal glomeruli   (MGI Ref ID J:67157)
  • abnormal ureteric bud morphology   (MGI Ref ID J:67157)
    • impaired branching involved in ureteric bud morphogenesis   (MGI Ref ID J:67157)
  • decreased kidney cell proliferation
    • at E15.5, no proliferating cells were observed inside the abnormal glomeruli whereas these cells were detected in control mice   (MGI Ref ID J:67157)
  • increased kidney apoptosis
    • at E15.5, an increased number of apoptotic cells was observed in the kidney of apoptotic cells in the kidney were observed   (MGI Ref ID J:67157)
  • kidney microaneurysm
    • the glomerular capillary tuft sometimes appears as a capillary aneurysm-like structure that releases red blood cells into the Bowman's capsule   (MGI Ref ID J:67157)
  • small kidney
    • at E16.5, kidneys were smaller than controls   (MGI Ref ID J:67157)
    • renal hypoplasia   (MGI Ref ID J:67157)
  • cardiovascular system phenotype
  • abnormal glomerular capillary endothelium morphology
    • few endothelial cells were present in the abnormal mutant glomeruli   (MGI Ref ID J:67157)
  • abnormal myocardial trabeculae morphology
    • reduced myocardial trabeculation evident by E12.5 and thereafter   (MGI Ref ID J:67157)
  • heart hypoplasia
    • in embryos surviving past E11.5, myocardial hypoplasia is evident, with hemorrhaging and edema   (MGI Ref ID J:67157)
  • hemorrhage
    • 40% of embryos exhibited widespread hemorrhaging at E11.5; also evident in later embryonic stages   (MGI Ref ID J:67157)
  • kidney microaneurysm
    • the glomerular capillary tuft sometimes appears as a capillary aneurysm-like structure that releases red blood cells into the Bowman's capsule   (MGI Ref ID J:67157)
  • pericardial effusion
    • 40% of embryos exhibited pericardial effusion at E11.5   (MGI Ref ID J:67157)
  • vision/eye phenotype
  • abnormal eye morphology
    • pronounced asymmetry of the eyes   (MGI Ref ID J:67157)
    • abnormal hyaloid artery morphology
      • aberrant bulbous structure at the terminus of the hyaloid artery, with many small capillaries emanating from it   (MGI Ref ID J:67157)
    • microphthalmia
      • bilateral   (MGI Ref ID J:67157)
    • persistent hyperplastic primary vitreous
      • retrolenticular hyperplasia   (MGI Ref ID J:67157)
  • homeostasis/metabolism phenotype
  • pericardial effusion
    • 40% of embryos exhibited pericardial effusion at E11.5   (MGI Ref ID J:67157)
  • skin edema
    • 50% of embryos at E13.5 showed edema and hemorrhaging vessels near skin surface   (MGI Ref ID J:67157)
  • growth/size/body phenotype
  • embryonic growth retardation
    • by E11.5, 40% of embryos showed growth retardation   (MGI Ref ID J:67157)
  • liver/biliary system phenotype
  • abnormal bile duct development
    • bile duct epithelial cell differentiation defects occur   (MGI Ref ID J:74574)
  • muscle phenotype
  • abnormal myocardial trabeculae morphology
    • reduced myocardial trabeculation evident by E12.5 and thereafter   (MGI Ref ID J:67157)
  • embryogenesis phenotype
  • embryonic growth retardation
    • by E11.5, 40% of embryos showed growth retardation   (MGI Ref ID J:67157)
  • endocrine/exocrine gland phenotype
  • abnormal bile duct development
    • bile duct epithelial cell differentiation defects occur   (MGI Ref ID J:74574)
  • integument phenotype
  • skin edema
    • 50% of embryos at E13.5 showed edema and hemorrhaging vessels near skin surface   (MGI Ref ID J:67157)
  • cellular phenotype
  • decreased kidney cell proliferation
    • at E15.5, no proliferating cells were observed inside the abnormal glomeruli whereas these cells were detected in control mice   (MGI Ref ID J:67157)
  • increased kidney apoptosis
    • at E15.5, an increased number of apoptotic cells was observed in the kidney of apoptotic cells in the kidney were observed   (MGI Ref ID J:67157)
View Research Applications

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

Cardiovascular Research
Vascular Defects

Developmental Biology Research
Eye Defects
Internal/Organ Defects
      heart
      heart: vasculature
      kidney
      vasculature
Perinatal Lethality
      Homozygous

Internal/Organ Research
Heart Abnormalities
Kidney Defects

Sensorineural Research
Eye Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Notch2tm1Grid
Allele Name targeted mutation 1, Tom Gridley
Allele Type Targeted (Hypomorph)
Common Name(s) Notch2-; Notch2del1;
Mutation Made By Tom Gridley,   Maine Medical Center Research Institute
Strain of Origin129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name Notch2, notch 2
Chromosome 3
Gene Common Name(s) AGS2; AI853703; HJCYS; Motch B; N2; expressed sequence AI853703; hN2;
Molecular Note This is a hypomorphic allele. A neomycin resistance cassette replaced 0.4 kb of sequence, including part of the exon encoding EGF repeat 14, the splice donor site at the 3' end of this exon, and 0.3 kb of intron. mRNA species are detected in homozygousmutant embryos that appear to be the result of inframe splicing around the neomycin cassette. Proteins derived from these transcripts are predicted to have a deletion of one or two EGF repeats. [MGI Ref ID J:67157]

Genotyping

Genotyping Information

Genotyping Protocols

Notch2tm1Grid, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

McCright B; Gao X; Shen L; Lozier J; Lan Y; Maguire M; Herzlinger D; Weinmaster G; Jiang R; Gridley T. 2001. Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation. Development 128(4):491-502. [PubMed: 11171333]  [MGI Ref ID J:67157]

Additional References

Notch2tm1Grid related

Krebs LT; Iwai N; Nonaka S; Welsh IC; Lan Y; Jiang R; Saijoh Y; O'Brien TP; Hamada H; Gridley T. 2003. Notch signaling regulates left-right asymmetry determination by inducing Nodal expression. Genes Dev 17(10):1207-12. [PubMed: 12730124]  [MGI Ref ID J:83358]

Loomes KM; Russo P; Ryan M; Nelson A; Underkoffler L; Glover C; Fu H; Gridley T; Kaestner KH; Oakey RJ. 2007. Bile duct proliferation in liver-specific Jag1 conditional knockout mice: effects of gene dosage. Hepatology 45(2):323-30. [PubMed: 17366661]  [MGI Ref ID J:149131]

Lozier J; McCright B; Gridley T. 2008. Notch signaling regulates bile duct morphogenesis in mice. PLoS ONE 3(3):e1851. [PubMed: 18365007]  [MGI Ref ID J:133171]

McCright B; Lozier J; Gridley T. 2002. A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency. Development 129(4):1075-82. [PubMed: 11861489]  [MGI Ref ID J:74574]

Meyer-Bahlburg A; Andrews SF; Yu KO; Porcelli SA; Rawlings DJ. 2008. Characterization of a late transitional B cell population highly sensitive to BAFF-mediated homeostatic proliferation. J Exp Med 205(1):155-68. [PubMed: 18180309]  [MGI Ref ID J:131142]

Nadeau JH. 2003. Modifier genes and protective alleles in humans and mice. Curr Opin Genet Dev 13(3):290-5. [PubMed: 12787792]  [MGI Ref ID J:88012]

You Y; Myers RC; Freeberg L; Foote J; Kearney JF; Justement LB; Carter RH. 2011. Marginal zone B cells regulate antigen capture by marginal zone macrophages. J Immunol 186(4):2172-81. [PubMed: 21257969]  [MGI Ref ID J:168986]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes die within a day of birth.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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, 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.

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