Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   10-SEP-10 Species laboratory mouse Generation F?+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.

Socs3^tm1Ayos/Socs3^tm1Ayos Lyz2^tm1(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)

Socs3^tm1Ayos/Socs3^tm1Ayos 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 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)

Socs3^tm1Ayos/Socs3^tm1Ayos 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 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 and Inflammation Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Socs3tm1Ayos
Allele Name		targeted mutation 1, Akihiko Yoshimura
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Socs3fl; Socs3flox;
Mutation Made By		Akihiko Yoshimura,   Kyushu Universtiy
Strain of Origin		129S4/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

Socs3^tm1Ayos, 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

Socs3^tm1Ayos 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]

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]

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]

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]

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           AX11

Colony Maintenance

Breeding & Husbandry	While maintaining a live colony, these mice are bred as either heterozygotes or homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   10-SEP-10
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

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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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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