Strain Name:

B6;129S4-Socs3tm1Ayos/J

Stock Number:

010944

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Availability:

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These suppressor of cytokine signaling 3 (Socs3)-floxed mice may be useful in generating conditional mutations to study cytokine signaling, inflammatory responses, energy homeostasis and diabetes.

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)   10-SEP-10
Specieslaboratory mouse
GenerationF?+N1F8 (02-MAY-13)
Generation Definitions
 
Donating Investigator Eleftheria Maratos-Flier,   Beth Israel Deaconess Medical Center, Harvard Medical School

Description
Mice that are homozygous for the targeted mutation are viable, fertile and normal in size. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of the floxed allele. This mutant mouse strain may be useful in generating conditional mutations to study cytokine signaling, inflammatory responses, energy homeostasis and diabetes.

For example, when crossed to a strain expressing Cre recombinase in the myeloid cell lineage (see Stock No. 004781), this mutant mouse strain may be useful in studies of cytokine signalling and inflammation.

When crossed to a strain expressing Cre recombinase in the central and peripheral nervous system (see Stock No. 003771), this mutant mouse strain may be useful in studies of leptin sensitivity and obesity.

When crossed to a strain expressing Cre recombinase in neuronal cells (see Stock No. 003966), this mutant mouse strain may be useful in studies of leptin sensitivity and obesity.

Development
A targeting vector was designed to place loxP sites in intron 1 and the 3' untranslated region of exon 2 of the targeted gene. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were used to generate chimeric mice and crossed to C57BL/6. Heterozygotes were intercrossed to maintain the colony. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Control Information

  Control
   101043 B6129SF1/J (approximate)
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.

Socs3tm1Ayos/Socs3tm1Ayos Lyz2tm1(cre)Ifo/Lyz2+

        involves: 129 * C57BL/6   (conditional)
  • immune system phenotype
  • decreased susceptibility to endotoxin shock
    • mutants are more resistant to LPS induced endotoxin shock   (MGI Ref ID J:92040)

Socs3tm1Ayos/Socs3tm1Ayos Tg(Nes-cre)1Kln/0

        involves: 129 * C57BL/6   (conditional)
  • adipose tissue phenotype
  • abnormal adipose tissue amount
    • on a high fat diet total fat weight and individual fat pad weights increase less in mutants compared to wild-type mice   (MGI Ref ID J:91796)
  • behavior/neurological phenotype
  • abnormal food intake
    • food intake is decreased on a high fat diet compared to wild-type mice on the same diet   (MGI Ref ID J:91796)
    • leptin treatment induces a greater decrease in food intake in mutants compared to wild-type mice   (MGI Ref ID J:91796)
  • growth/size/body phenotype
  • decreased body weight
    • on a high fat diet mutants gain less weight   (MGI Ref ID J:91796)
    • weight loss
      • treatment with leptin induces greater weight loss in mutants   (MGI Ref ID J:91796)
  • homeostasis/metabolism phenotype
  • decreased circulating free fatty acid level
    • after 22 weeks on a high fat diet plasma free fatty acid levels are significantly lower in mutants   (MGI Ref ID J:91796)
  • decreased circulating triglyceride level
    • after 22 weeks on a high fat diet triglyceride levels are significantly lower in mutants   (MGI Ref ID J:91796)
  • improved glucose tolerance
    • glucose clearance is significantly faster in mutants compared to wild-type mice   (MGI Ref ID J:91796)
  • increased insulin sensitivity
    • on a high fat diet mutants do not develop insulin resistance   (MGI Ref ID J:91796)

Socs3tm1Ayos/Socs3tm1Ayos Tg(Syn1-cre)671Jxm/0

        involves: 129 * C57BL/6   (conditional)
  • adipose tissue phenotype
  • abnormal adipose tissue amount
    • on a high fat diet total fat weight and individual fat pad weights increase less in mutants compared to wild-type mice   (MGI Ref ID J:91796)
  • behavior/neurological phenotype
  • abnormal food intake
    • food intake is decreased on a high fat diet compared to wild-type mice on the same diet   (MGI Ref ID J:91796)
    • leptin treatment induces a greater decrease in food intake in mutants compared to wild-type mice   (MGI Ref ID J:91796)
  • growth/size/body phenotype
  • decreased body weight
    • on a high fat diet mutants gain less weight   (MGI Ref ID J:91796)
    • weight loss
      • treatment with leptin induces greater weight loss in mutants   (MGI Ref ID J:91796)
  • homeostasis/metabolism phenotype
  • decreased circulating free fatty acid level
    • after 22 weeks on a high fat diet plasma free fatty acid levels are significantly lower in mutants   (MGI Ref ID J:91796)
  • decreased circulating triglyceride level
    • after 22 weeks on a high fat diet triglyceride levels are significantly lower in mutants   (MGI Ref ID J:91796)
  • improved glucose tolerance
    • glucose clearance is significantly faster in mutants compared to wild-type mice   (MGI Ref ID J:91796)
  • increased insulin sensitivity
    • on a high fat diet mutants do not develop insulin resistance   (MGI Ref ID J:91796)
View Research Applications

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

Research Tools
Cre-lox System
      loxP-flanked Sequences
Diabetes and Obesity Research
      loxP
Immunology, Inflammation and Autoimmunity Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Socs3tm1Ayos
Allele Name targeted mutation 1, Akihiko Yoshimura
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) Socs3fl; Socs3flox;
Mutation Made By Akihiko Yoshimura,   Kyushu Universtiy
Strain of Origin129S4/SvJae
Gene Symbol and Name Socs3, suppressor of cytokine signaling 3
Chromosome 11
Gene Common Name(s) ATOD4; CIS3; Cish3; E2a-Pbx1 target gene in fibroblasts 10; EF-10; SOCS-3; SSI-3; SSI3; STAT-induced STAT inhibitor 3; cytokine inducible SH2-containing protein 3; cytokine-inducible SH2 protein 3;
Molecular Note Loxp sites were inserted in intron 1 and in the 3' UTR of exon 2, thereby surrounding the coding sequence. Southern blot confirmed recombination. [MGI Ref ID J:92040]

Genotyping

Genotyping Information

Genotyping Protocols

Socs3tm1Ayos, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Yasukawa H; Ohishi M; Mori H; Murakami M; Chinen T; Aki D; Hanada T; Takeda K; Akira S; Hoshijima M; Hirano T; Chien KR; Yoshimura A. 2003. IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages. Nat Immunol 4(6):551-6. [PubMed: 12754507]  [MGI Ref ID J:92040]

Additional References

Socs3tm1Ayos related

Briancon N; McNay DE; Maratos-Flier E; Flier JS. 2010. Combined neural inactivation of suppressor of cytokine signaling-3 and protein-tyrosine phosphatase-1B reveals additive, synergistic, and factor-specific roles in the regulation of body energy balance. Diabetes 59(12):3074-84. [PubMed: 20876718]  [MGI Ref ID J:169330]

Chen Z; Laurence A; Kanno Y; Pacher-Zavisin M; Zhu BM; Tato C; Yoshimura A; Hennighausen L; O'Shea JJ. 2006. Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci U S A 103(21):8137-42. [PubMed: 16698929]  [MGI Ref ID J:110219]

Fischer P; Lehmann U; Sobota RM; Schmitz J; Niemand C; Linnemann S; Haan S; Behrmann I; Yoshimura A; Johnston JA; Muller-Newen G; Heinrich PC; Schaper F. 2004. The role of the inhibitors of interleukin-6 signal transduction SHP2 and SOCS3 for desensitization of interleukin-6 signalling. Biochem J 378(Pt 2):449-60. [PubMed: 14611646]  [MGI Ref ID J:113612]

Fukuda S; Abematsu M; Mori H; Yanagisawa M; Kagawa T; Nakashima K; Yoshimura A; Taga T. 2007. Potentiation of astrogliogenesis by STAT3-mediated activation of bone morphogenetic protein-Smad signaling in neural stem cells. Mol Cell Biol 27(13):4931-7. [PubMed: 17452461]  [MGI Ref ID J:122731]

Hiwatashi K; Tamiya T; Hasegawa E; Fukaya T; Hashimoto M; Kakoi K; Kashiwagi I; Kimura A; Inoue N; Morita R; Yasukawa H; Yoshimura A. 2011. Suppression of SOCS3 in macrophages prevents cancer metastasis by modifying macrophage phase and MCP2/CCL8 induction. Cancer Lett 308(2):172-80. [PubMed: 21624767]  [MGI Ref ID J:173608]

Inagaki-Ohara K; Mayuzumi H; Kato S; Minokoshi Y; Otsubo T; Kawamura YI; Dohi T; Matsuzaki G; Yoshimura A. 2014. Enhancement of leptin receptor signaling by SOCS3 deficiency induces development of gastric tumors in mice. Oncogene 33(1):74-84. [PubMed: 23178499]  [MGI Ref ID J:204880]

Kievit P; Howard JK; Badman MK; Balthasar N; Coppari R; Mori H; Lee CE; Elmquist JK; Yoshimura A; Flier JS. 2006. Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells. Cell Metab 4(2):123-32. [PubMed: 16890540]  [MGI Ref ID J:129732]

Kimura A; Kinjyo I; Matsumura Y; Mori H; Mashima R; Harada M; Chien KR; Yasukawa H; Yoshimura A. 2004. SOCS3 is a physiological negative regulator for granulopoiesis and granulocyte colony-stimulating factor receptor signaling. J Biol Chem 279(8):6905-10. [PubMed: 14699146]  [MGI Ref ID J:88961]

Kinjyo I; Inoue H; Hamano S; Fukuyama S; Yoshimura T; Koga K; Takaki H; Himeno K; Takaesu G; Kobayashi T; Yoshimura A. 2006. Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-beta 1. J Exp Med 203(4):1021-31. [PubMed: 16606674]  [MGI Ref ID J:123779]

Lesina M; Kurkowski MU; Ludes K; Rose-John S; Treiber M; Kloppel G; Yoshimura A; Reindl W; Sipos B; Akira S; Schmid RM; Algul H. 2011. Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell 19(4):456-69. [PubMed: 21481788]  [MGI Ref ID J:170981]

Lu Y; Fukuyama S; Yoshida R; Kobayashi T; Saeki K; Shiraishi H; Yoshimura A; Takaesu G. 2006. Loss of SOCS3 gene expression converts STAT3 function from anti-apoptotic to pro-apoptotic. J Biol Chem 281(48):36683-90. [PubMed: 17028185]  [MGI Ref ID J:117662]

Matarazzo V; Schaller F; Nedelec E; Benani A; Penicaud L; Muscatelli F; Moyse E; Bauer S. 2012. Inactivation of Socs3 in the hypothalamus enhances the hindbrain response to endogenous satiety signals via oxytocin signaling. J Neurosci 32(48):17097-107. [PubMed: 23197703]  [MGI Ref ID J:192802]

Matsumura Y; Kobayashi T; Ichiyama K; Yoshida R; Hashimoto M; Takimoto T; Tanaka K; Chinen T; Shichita T; Wyss-Coray T; Sato K; Yoshimura A. 2007. Selective expansion of foxp3-positive regulatory T cells and immunosuppression by suppressors of cytokine signaling 3-deficient dendritic cells. J Immunol 179(4):2170-9. [PubMed: 17675476]  [MGI Ref ID J:151229]

Mori H; Hanada R; Hanada T; Aki D; Mashima R; Nishinakamura H; Torisu T; Chien KR; Yasukawa H; Yoshimura A. 2004. Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat Med 10(7):739-43. [PubMed: 15208705]  [MGI Ref ID J:91796]

Mori H; Shichita T; Yu Q; Yoshida R; Hashimoto M; Okamoto F; Torisu T; Nakaya M; Kobayashi T; Takaesu G; Yoshimura A. 2007. Suppression of SOCS3 expression in the pancreatic beta-cell leads to resistance to type 1 diabetes. Biochem Biophys Res Commun 359(4):952-8. [PubMed: 17562326]  [MGI Ref ID J:122729]

Ogata H; Kobayashi T; Chinen T; Takaki H; Sanada T; Minoda Y; Koga K; Takaesu G; Maehara Y; Iida M; Yoshimura A. 2006. Deletion of the SOCS3 gene in liver parenchymal cells promotes hepatitis-induced hepatocarcinogenesis. Gastroenterology 131(1):179-93. [PubMed: 16831601]  [MGI Ref ID J:116784]

Ohishi M; Matsumura Y; Aki D; Mashima R; Taniguchi K; Kobayashi T; Kukita T; Iwamoto Y; Yoshimura A. 2005. Suppressors of cytokine signaling-1 and -3 regulate osteoclastogenesis in the presence of inflammatory cytokines. J Immunol 174(5):3024-31. [PubMed: 15728516]  [MGI Ref ID J:97719]

Okada S; Nakamura M; Katoh H; Miyao T; Shimazaki T; Ishii K; Yamane J; Yoshimura A; Iwamoto Y; Toyama Y; Okano H. 2006. Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nat Med 12(7):829-34. [PubMed: 16783372]  [MGI Ref ID J:111976]

Ozawa Y; Nakao K; Kurihara T; Shimazaki T; Shimmura S; Ishida S; Yoshimura A; Tsubota K; Okano H. 2008. Roles of STAT3/SOCS3 pathway in regulating the visual function and ubiquitin-proteasome-dependent degradation of rhodopsin during retinal inflammation. J Biol Chem 283(36):24561-70. [PubMed: 18614536]  [MGI Ref ID J:142014]

Ozawa Y; Nakao K; Shimazaki T; Shimmura S; Kurihara T; Ishida S; Yoshimura A; Tsubota K; Okano H. 2007. SOCS3 is required to temporally fine-tune photoreceptor cell differentiation. Dev Biol 303(2):591-600. [PubMed: 17198696]  [MGI Ref ID J:119192]

Qin S; Zou Y; Zhang CL. 2013. Cross-talk between KLF4 and STAT3 regulates axon regeneration. Nat Commun 4:2633. [PubMed: 24129709]  [MGI Ref ID J:206059]

Robinson GW; Pacher-Zavisin M; Zhu BM; Yoshimura A; Hennighausen L. 2007. Socs 3 modulates the activity of the transcription factor Stat3 in mammary tissue and controls alveolar homeostasis. Dev Dyn 236(3):654-61. [PubMed: 17205581]  [MGI Ref ID J:118349]

Smith PD; Sun F; Park KK; Cai B; Wang C; Kuwako K; Martinez-Carrasco I; Connolly L; He Z. 2009. SOCS3 deletion promotes optic nerve regeneration in vivo. Neuron 64(5):617-23. [PubMed: 20005819]  [MGI Ref ID J:155741]

Stahl A; Joyal JS; Chen J; Sapieha P; Juan AM; Hatton CJ; Pei DT; Hurst CG; Seaward MR; Krah NM; Dennison RJ; Greene ER; Boscolo E; Panigrahy D; Smith LE. 2012. SOCS3 is an endogenous inhibitor of pathologic angiogenesis. Blood 120(14):2925-9. [PubMed: 22791286]  [MGI Ref ID J:189163]

Stumhofer JS; Laurence A; Wilson EH; Huang E; Tato CM; Johnson LM; Villarino AV; Huang Q; Yoshimura A; Sehy D; Saris CJ; O'Shea JJ; Hennighausen L; Ernst M; Hunter CA. 2006. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol 7(9):937-45. [PubMed: 16906166]  [MGI Ref ID J:112649]

Taleb S; Romain M; Ramkhelawon B; Uyttenhove C; Pasterkamp G; Herbin O; Esposito B; Perez N; Yasukawa H; Van Snick J; Yoshimura A; Tedgui A; Mallat Z. 2009. Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis. J Exp Med 206(10):2067-77. [PubMed: 19737863]  [MGI Ref ID J:153361]

Torisu T; Sato N; Yoshiga D; Kobayashi T; Yoshioka T; Mori H; Iida M; Yoshimura A. 2007. The dual function of hepatic SOCS3 in insulin resistance in vivo. Genes Cells 12(2):143-54. [PubMed: 17295835]  [MGI Ref ID J:123391]

Xu L; Kitani A; Stuelten C; McGrady G; Fuss I; Strober W. 2010. Positive and negative transcriptional regulation of the Foxp3 gene is mediated by access and binding of the Smad3 protein to enhancer I. Immunity 33(3):313-25. [PubMed: 20870174]  [MGI Ref ID J:164648]

Yajima T; Murofushi Y; Zhou H; Park S; Housman J; Zhong ZH; Nakamura M; Machida M; Hwang KK; Gu Y; Dalton ND; Yajima T; Yasukawa H; Peterson KL; Knowlton KU. 2011. Absence of SOCS3 in the cardiomyocyte increases mortality in a gp130-dependent manner accompanied by contractile dysfunction and ventricular arrhythmias. Circulation 124(24):2690-701. [PubMed: 22082679]  [MGI Ref ID J:193801]

Yan C; Ward PA; Wang X; Gao H. 2013. Myeloid depletion of SOCS3 enhances LPS-induced acute lung injury through CCAAT/enhancer binding protein delta pathway. FASEB J 27(8):2967-76. [PubMed: 23585399]  [MGI Ref ID J:203576]

Young A; Linehan E; Hams E; O'Hara Hall AC; McClurg A; Johnston JA; Hunter CA; Fallon PG; Fitzgerald DC. 2012. Cutting edge: suppression of GM-CSF expression in murine and human T cells by IL-27. J Immunol 189(5):2079-83. [PubMed: 22837488]  [MGI Ref ID J:189868]

Yu CR; Kim SH; Mahdi RM; Egwuagu CE. 2013. SOCS3 deletion in T lymphocytes suppresses development of chronic ocular inflammation via upregulation of CTLA-4 and expansion of regulatory T cells. J Immunol 191(10):5036-43. [PubMed: 24101549]  [MGI Ref ID J:206335]

Zhang H; Neuhofer P; Song L; Rabe B; Lesina M; Kurkowski MU; Treiber M; Wartmann T; Regner S; Thorlacius H; Saur D; Weirich G; Yoshimura A; Halangk W; Mizgerd JP; Schmid RM; Rose-John S; Algul H. 2013. IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality. J Clin Invest 123(3):1019-31. [PubMed: 23426178]  [MGI Ref ID J:196394]

Zhang R; Dhillon H; Yin H; Yoshimura A; Lowell BB; Maratos-Flier E; Flier JS. 2008. Selective inactivation of Socs3 in SF1 neurons improves glucose homeostasis without affecting body weight. Endocrinology 149(11):5654-61. [PubMed: 18669597]  [MGI Ref ID J:145473]

Zhu BM; Ishida Y; Robinson GW; Pacher-Zavisin M; Yoshimura A; Murphy PM; Hennighausen L. 2008. SOCS3 negatively regulates the gp130-STAT3 pathway in mouse skin wound healing. J Invest Dermatol 128(7):1821-9. [PubMed: 18185532]  [MGI Ref ID J:137538]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhile maintaining a live colony, these mice are bred as either heterozygotes or homozygotes.
Mating SystemHomozygote x Homozygote         (Female x Male)   10-SEP-10
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 Socs3tm1Ayos  
Price per Pair (US dollars $)Pair Genotype
$478.00Homozygous for Socs3tm1Ayos x Homozygous for Socs3tm1Ayos  

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 Socs3tm1Ayos  
Price per Pair (US dollars $)Pair Genotype
$621.40Homozygous for Socs3tm1Ayos x Homozygous for Socs3tm1Ayos  

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
   101043 B6129SF1/J (approximate)
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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