Strain Name:

C.129S2-Stat4tm1Gru/J

Stock Number:

002826

Availability:

Repository- Live

Use Restrictions Apply, see Terms of Use

Description

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.
Mating SystemHomozygote x Homozygote         (Female x Male)
Specieslaboratory mouse
Background Strain BALB/c
Donor Strain 129S2 via D3 ES cell line
GenerationN10F24 (03-DEC-08)
 
Donating Investigator Michael Grusby,   Harvard Medical School

Appearance
albino
Related Genotype: A/A Tyrp1b/Tyrp1b Tyrc/Tyrc

Description
Mice homozygous for the Stat4tm1Gru mutation are viable and fertile. IL12 induced interferon-gamma secretion and stimulation of lymphocytes are defective. Development of Th1 cells in response to either IL12 or Listeria monocytogenes is also defective with propensity towards Th2 cells.

Control Information

  Control
   000651 BALB/cJ
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Stat4tm1Gru allele
003750   C.129S2-Stat4tm1Gru Stat6tm1Gru/J
004671   NOD.129S2-Stat4tm1Gru/JbsJ
View Strains carrying   Stat4tm1Gru     (2 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms
NOTDiabetes Mellitus, Insulin-Dependent; IDDM - No similarity to the expected human disease phenotype was found.4
Diabetes Mellitus, Insulin-Dependent; IDDM - Models with phenotypic similarity to human disease where etiologies are distinct.2
2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).
4 One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of those genes, but the phenotype did not resemble the disease.
View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Stat4tm1Gru/Stat4tm1Gru

        C.129S2-Stat4tm1Gru
  • immune system phenotype
  • decreased circulating interferon-gamma level (MGI Ref ID J:90600)
    • reduction in the serum level of IFNG are seen compared to levels in diabetic and non-diabetic NOD mice, but serum level is comparable to that in Stat4-null NOD mice
  • decreased circulating interleukin-2 level (MGI Ref ID J:90600)
    • reduction in the serum level of IL-2 is seen compared to level in diabetic and non-diabetic NOD mice, but serum level of IL-12 is comparable to that of Stat4-null NOD mice
  • homeostasis/metabolism phenotype
  • decreased circulating interferon-gamma level (MGI Ref ID J:90600)
    • reduction in the serum level of IFNG are seen compared to levels in diabetic and non-diabetic NOD mice, but serum level is comparable to that in Stat4-null NOD mice
  • decreased circulating interleukin-2 level (MGI Ref ID J:90600)
    • reduction in the serum level of IL-2 is seen compared to level in diabetic and non-diabetic NOD mice, but serum level of IL-12 is comparable to that of Stat4-null NOD mice

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

Stat4tm1Gru/Stat4+

        NOD.129S2-Stat4tm1Gru
  • homeostasis/metabolism phenotype
  • abnormal circulating glucose level (MGI Ref ID J:90600)
    • a significant decrease in the incidence of diabetes (30%) is observed compared with wild-type Stat4 NOD mice (74%); diabetes is diagnosed when 3 blood glucose measures are equal to or higher than 13.9 mmol/l

Stat4tm1Gru/Stat4tm1Gru

        involves: 129S2/SvPas * BALB/c
  • immune system phenotype
  • abnormal lymphocyte physiology (MGI Ref ID J:34059)
    • abnormal NK cell physiology (MGI Ref ID J:34059)
      • IL-12 stimulated NK cells do not show enhanced cytotoxicity compared to unstimulated cells, while stimulated control cells show a significant enhancement (30% specific lysis compared to 10% in unstimulated control cells)
    • abnormal T cell proliferation (MGI Ref ID J:34059)
      • activated T lymphocytes stimulated with IL-12 for 48 hours do not proliferate, whereas activated lymphocytes from control mice exhibit dose-dependent proliferation
    • abnormal T-helper 1 physiology (MGI Ref ID J:34059)
      • cultured lymphocytes differentiated into Th1 cells by anti-CD3 or heat-killed Listeria monocytogenes produce less than 20% of the IFNG produced by control cells; lymphotoxin production also is significantly reduced compared to control cells
      • significant levels of Th2 cytokines IL-5 and IL-10 are detected in supernatants from these cultured lymphocytes
    • abnormal T-helper 2 physiology (MGI Ref ID J:34059)
      • lymphocytes cultured in the presence of IL-4 and IFNG produce significantly higher levels of Th2 cytokines than control cells
  • decreased interferon-gamma secretion (MGI Ref ID J:34059)
    • following Il-2 stimulation for 24 hours, lymphocytes from mutants do not show increased IFNG levels compared to a 15-fold increase seen in activated cells from control mice
  • hematopoietic system phenotype
  • abnormal T cell proliferation (MGI Ref ID J:34059)
    • activated T lymphocytes stimulated with IL-12 for 48 hours do not proliferate, whereas activated lymphocytes from control mice exhibit dose-dependent proliferation

Stat4tm1Gru/Stat4tm1Gru

        NOD.129S2-Stat4tm1Gru
  • immune system phenotype
  • abnormal inflammatory response (MGI Ref ID J:90600)
    • noc cellular infiltration is observed at 40 weeks of age compared to massive and invasive cellular infiltration seen in diabetic NOD controls and heterozygous Stat4 NOD or wild-type Stat4 mice
    • a significant reduction in the numbers of CD4+ and CD8+ cells in islets is observed compared to diabetic NOD mice
    • decreased circulating interferon-gamma level (MGI Ref ID J:90600)
      • reduction in the serum level of IFNG is seen compared to diabetic and non-diabetic NOD mice
    • decreased circulating interleukin-2 level (MGI Ref ID J:90600)
      • a reduction in the serum level of IL-2 is observed compared to diabetic and non-diabetic NOD mice
  • decreased susceptibility to autoimmune diabetes (MGI Ref ID J:90600)
    • no female mutants develop diabetes (blood glucose levels above 13.9 mmol/l for 3 readings) over a 10-month period compared with 74% of female wild-type Stat4 NOD mice, which is similar to female NOD mice (80%)
  • endocrine/exocrine gland phenotype
  • abnormal insulin secretion (MGI Ref ID J:90600)
    • compared to NOD controls, islets in Stat4 null NOD mice show well preserved insulin secretion at basal glucose levels and in response to high glucose
  • abnormal pancreatic beta cell morphology (MGI Ref ID J:90600)
    • well-preserved insulin-positive cells are seen in the islets of mutants whereas such cells are rare in Stat4 heterozygous and wild-type Stat4 NOD mice
  • digestive/alimentary phenotype
  • abnormal insulin secretion (MGI Ref ID J:90600)
    • compared to NOD controls, islets in Stat4 null NOD mice show well preserved insulin secretion at basal glucose levels and in response to high glucose
  • abnormal pancreatic beta cell morphology (MGI Ref ID J:90600)
    • well-preserved insulin-positive cells are seen in the islets of mutants whereas such cells are rare in Stat4 heterozygous and wild-type Stat4 NOD mice
  • homeostasis/metabolism phenotype
  • decreased circulating interferon-gamma level (MGI Ref ID J:90600)
    • reduction in the serum level of IFNG is seen compared to diabetic and non-diabetic NOD mice
  • decreased circulating interleukin-2 level (MGI Ref ID J:90600)
    • a reduction in the serum level of IL-2 is observed compared to diabetic and non-diabetic NOD mice
View Research Applications

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

Stat4tm1Gru related

Immunology and Inflammation Research
Immunodeficiency
Intracellular Signaling Molecules

Genes & Alleles

Gene & Allele Information

 
Allele Symbol Stat4tm1Gru
Allele Name targeted mutation 1, Michael J Grusby
Allele Type Targeted (knock-out)
Common Name(s) Stat4-;
Mutation Made By Michael Grusby,   Harvard Medical School
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Stat4, signal transducer and activator of transcription 4
Chromosome 1
Gene Common Name(s) SLEB11;
Molecular Note The exon encoding amino acids 263 through 314 was disrupted by the insertion of a neomycin selection cassette. The encoded protein was undetectable in the thymi and lymph nodes of homozygous mutant mice by immunoblot analysis. [MGI Ref ID J:34059]

Genotyping

Genotyping Information

Genotyping Protocols

Stat4tm1Gru, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Kaplan MH; Sun YL; Hoey T; Grusby MJ. 1996. Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature 382(6587):174-7. [PubMed: 8700209]  [MGI Ref ID J:34059]

Additional References

Chi H; Lu B; Takekawa M; Davis RJ; Flavell RA. 2004. GADD45beta/GADD45gamma and MEKK4 comprise a genetic pathway mediating STAT4-independent IFNgamma production in T cells. EMBO J 23(7):1576-86. [PubMed: 15044949]  [MGI Ref ID J:90112]

Deng JC; Zeng X; Newstead M; Moore TA; Tsai WC; Thannickal VJ; Standiford TJ. 2004. STAT4 is a critical mediator of early innate immune responses against pulmonary Klebsiella infection. J Immunol 173(6):4075-83. [PubMed: 15356157]  [MGI Ref ID J:92750]

Grogan JL; Mohrs M; Harmon B; Lacy DA; Sedat JW; Locksley RM. 2001. Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity 14(3):205-15. [PubMed: 11290331]  [MGI Ref ID J:68346]

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]

Park WR; Nakahira M; Sugimoto N; Bian Y; Yashiro-Ohtani Y; Zhou XY; Yang YF; Hamaoka T; Fujiwara H. 2004. A mechanism underlying STAT4-mediated up-regulation of IFN-gamma induction inTCR-triggered T cells. Int Immunol 16(2):295-302. [PubMed: 14734615]  [MGI Ref ID J:88973]

Wang W; Ostlie NS; Conti-Fine BM; Milani M. 2004. The susceptibility to experimental myasthenia gravis of STAT6-/- and STAT4-/- BALB/c mice suggests a pathogenic role of Th1 cells. J Immunol 172(1):97-103. [PubMed: 14688314]  [MGI Ref ID J:87570]

Yang Z; Chen M; Ellett JD; Fialkow LB; Carter JD; McDuffie M; Nadler JL. 2004. Autoimmune diabetes is blocked in Stat4-deficient mice. J Autoimmun 22(3):191-200. [PubMed: 15041039]  [MGI Ref ID J:90600]

Stat4tm1Gru related

Afkarian M; Sedy JR; Yang J; Jacobson NG; Cereb N; Yang SY; Murphy TL; Murphy KM. 2002. T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nat Immunol 3(6):549-57. [PubMed: 12006974]  [MGI Ref ID J:109160]

Agarwal S; Rao A. 1998. Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity 9(6):765-75. [PubMed: 9881967]  [MGI Ref ID J:51833]

Armstrong BD; Abad C; Chhith S; Cheung-Lau G; Hajji OE; Coute AC; Ngo DH; Waschek JA. 2006. Impairment of axotomy-induced pituitary adenylyl cyclase-activating peptide gene expression in T helper 2 lymphocyte-deficient mice. Neuroreport 17(3):309-12. [PubMed: 16462603]  [MGI Ref ID J:106085]

Becskei A; Grusby MJ. 2007. Contribution of IL-12R mediated feedback loop to Th1 cell differentiation. FEBS Lett 581(27):5199-206. [PubMed: 17950290]  [MGI Ref ID J:127745]

Blum A; Setiawan T; Hang L; Stoyanoff K; Weinstock JV. 2008. Interleukin-12 (IL-12) and IL-23 induction of substance p synthesis in murine T cells and macrophages is subject to IL-10 and transforming growth factor beta regulation. Infect Immun 76(8):3651-6. [PubMed: 18505813]  [MGI Ref ID J:139373]

Broxmeyer HE; Bruns HA; Zhang S; Cooper S; Hangoc G; McKenzie AN; Dent AL; Schindler U; Naeger LK; Hoey T; Kaplan MH. 2002. Th1 cells regulate hematopoietic progenitor cell homeostasis by production of oncostatin m. Immunity 16(6):815-25. [PubMed: 12121663]  [MGI Ref ID J:77523]

Castilow EM; Legge KL; Varga SM. 2008. Cutting edge: Eosinophils do not contribute to respiratory syncytial virus vaccine-enhanced disease. J Immunol 181(10):6692-6. [PubMed: 18981084]  [MGI Ref ID J:140954]

Chang HC; Zhang S; Kaplan MH. 2002. Neonatal tolerance in the absence of Stat4- and Stat6- dependent Th cell differentiation. J Immunol 169(8):4124-8. [PubMed: 12370340]  [MGI Ref ID J:120160]

Chang HC; Zhang S; Oldham I; Naeger L; Hoey T; Kaplan MH. 2003. STAT4 requires the N-terminal domain for efficient phosphorylation. J Biol Chem 278(34):32471-7. [PubMed: 12805384]  [MGI Ref ID J:85186]

Chesler DA; Reiss CS. 2002. IL-12, while beneficial, is not essential for the host response to VSV encephalitis. J Neuroimmunol 131(1-2):92-7. [PubMed: 12458040]  [MGI Ref ID J:102956]

Chi H; Lu B; Takekawa M; Davis RJ; Flavell RA. 2004. GADD45beta/GADD45gamma and MEKK4 comprise a genetic pathway mediating STAT4-independent IFNgamma production in T cells. EMBO J 23(7):1576-86. [PubMed: 15044949]  [MGI Ref ID J:90112]

Chitnis T; Najafian N; Benou C; Salama AD; Grusby MJ; Sayegh MH; Khoury SJ. 2001. Effect of targeted disruption of STAT4 and STAT6 on the induction of experimental autoimmune encephalomyelitis. J Clin Invest 108(5):739-47. [PubMed: 11544280]  [MGI Ref ID J:71460]

Chitnis T; Salama AD; Grusby MJ; Sayegh MH; Khoury SJ. 2004. Defining Th1 and Th2 immune responses in a reciprocal cytokine environment in vivo. J Immunol 172(7):4260-5. [PubMed: 15034039]  [MGI Ref ID J:88725]

Chung DR; Kasper DL; Panzo RJ; Chtinis T; Grusby MJ; Sayegh MH; Tzianabos AO. 2003. CD4+ T cells mediate abscess formation in intra-abdominal sepsis by an IL-17-dependent mechanism. J Immunol 170(4):1958-63. [PubMed: 12574364]  [MGI Ref ID J:81809]

Croy BA; Ashkar AA; Foster RA; DiSanto JP; Magram J; Carson D; Gendler SJ; Grusby MJ; Wagner N; Muller W; Guimond MJ. 1997. Histological studies of gene-ablated mice support important functional roles for natural killer cells in the uterus during pregnancy J Reprod Immunol 35(2):111-33. [PubMed: 9421796]  [MGI Ref ID J:44813]

Curtsinger JM; Valenzuela JO; Agarwal P; Lins D; Mescher MF. 2005. Type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation. J Immunol 174(8):4465-9. [PubMed: 15814665]  [MGI Ref ID J:98161]

Deng JC; Zeng X; Newstead M; Moore TA; Tsai WC; Thannickal VJ; Standiford TJ. 2004. STAT4 is a critical mediator of early innate immune responses against pulmonary Klebsiella infection. J Immunol 173(6):4075-83. [PubMed: 15356157]  [MGI Ref ID J:92750]

Devoss JJ; Shum AK; Johannes KP; Lu W; Krawisz AK; Wang P; Yang T; Leclair NP; Austin C; Strauss EC; Anderson MS. 2008. Effector mechanisms of the autoimmune syndrome in the murine model of autoimmune polyglandular syndrome type 1. J Immunol 181(6):4072-9. [PubMed: 18768863]  [MGI Ref ID J:139094]

Elvin SJ; Williamson ED. 2004. Stat 4 but not Stat 6 mediated immune mechanisms are essential in protection against plague. Microb Pathog 37(4):177-84. [PubMed: 15458778]  [MGI Ref ID J:102018]

Eyles JL; Metcalf D; Grusby MJ; Hilton DJ; Starr R. 2002. Negative regulation of interleukin-12 signaling by suppressor of cytokine signaling-1. J Biol Chem 277(46):43735-40. [PubMed: 12221108]  [MGI Ref ID J:119132]

Fairweather D; Frisancho-Kiss S; Yusung SA; Barrett MA; Davis SE; Steele RA; Gatewood SJ; Rose NR. 2005. IL-12 protects against coxsackievirus B3-induced myocarditis by increasing IFN-gamma and macrophage and neutrophil populations in the heart. J Immunol 174(1):261-9. [PubMed: 15611248]  [MGI Ref ID J:95857]

Finnegan A; Grusby MJ; Kaplan CD; O'Neill SK; Eibel H; Koreny T; Czipri M; Mikecz K; Zhang J. 2002. IL-4 and IL-12 regulate proteoglycan-induced arthritis through Stat-dependent mechanisms. J Immunol 169(6):3345-52. [PubMed: 12218156]  [MGI Ref ID J:120443]

Fraidakis MJ; Kiyotani T; Pernold K; Bergstrom J; Olson L. 2007. Recovery from spinal cord injury in tumor necrosis factor-alpha, signal transducers and activators of transcription 4 and signal transducers and activators of transcription 6 null mice. Neuroreport 18(2):185-9. [PubMed: 17301687]  [MGI Ref ID J:120345]

Freudenberg MA; Merlin T; Kalis C; Chvatchko Y; Stubig H; Galanos C. 2002. Cutting edge: a murine, IL-12-independent pathway of IFN-gamma induction by gram-negative bacteria based on STAT4 activation by Type I IFN and IL-18 signaling. J Immunol 169(4):1665-8. [PubMed: 12165484]  [MGI Ref ID J:120706]

Furuta S; Kagami S; Tamachi T; Ikeda K; Fujiwara M; Suto A; Hirose K; Watanabe N; Saito Y; Iwamoto I; Nakajima H. 2008. Overlapping and distinct roles of STAT4 and T-bet in the regulation of T cell differentiation and allergic airway inflammation. J Immunol 180(10):6656-62. [PubMed: 18453585]  [MGI Ref ID J:134955]

Godshall CJ; Lentsch AB; Peyton JC; Scott MJ; Cheadle WG. 2001. STAT4 is required for antibacterial defense but enhances mortality during polymicrobial sepsis. Clin Diagn Lab Immunol 8(6):1044-8. [PubMed: 11687437]  [MGI Ref ID J:102411]

Grabie N; Delfs MW; Westrich JR; Love VA; Stavrakis G; Ahmad F; Seidman CE; Seidman JG; Lichtman AH. 2003. IL-12 is required for differentiation of pathogenic CD8+ T cell effectors that cause myocarditis. J Clin Invest 111(5):671-80. [PubMed: 12618521]  [MGI Ref ID J:132693]

Harris DP; Goodrich S; Gerth AJ; Peng SL; Lund FE. 2005. Regulation of IFN-gamma production by B effector 1 cells: essential roles for T-bet and the IFN-gamma receptor. J Immunol 174(11):6781-90. [PubMed: 15905519]  [MGI Ref ID J:99038]

Herold KC; Lu J; Rulifson I; Vezys V; Taub D; Grusby MJ; Bluestone JA. 1997. Regulation of C-C chemokine production by murine T cells by CD28/B7 costimulation. J Immunol 159(9):4150-3. [PubMed: 9379007]  [MGI Ref ID J:110673]

Hoey T; Zhang S; Schmidt N; Yu Q; Ramchandani S; Xu X; Naeger LK; Sun YL; Kaplan MH. 2003. Distinct requirements for the naturally occurring splice forms Stat4alpha and Stat4beta in IL-12 responses. EMBO J 22(16):4237-48. [PubMed: 12912921]  [MGI Ref ID J:130992]

Holz A; Bot A; Coon B; Wolfe T; Grusby MJ; von Herrath MG. 1999. Disruption of the STAT4 signaling pathway protects from autoimmune diabetes while retaining antiviral immune competence. J Immunol 163(10):5374-82. [PubMed: 10553062]  [MGI Ref ID J:107047]

Huber SA; Sakkinen P; David C; Newell MK; Tracy RP. 2001. T helper-cell phenotype regulates atherosclerosis in mice under conditions of mild hypercholesterolemia. Circulation 103(21):2610-6. [PubMed: 11382732]  [MGI Ref ID J:133189]

Jacob CO; Zang S; Li L; Ciobanu V; Quismorio F; Mizutani A; Satoh M; Koss M. 2003. Pivotal role of Stat4 and Stat6 in the pathogenesis of the lupus-like disease in the New Zealand mixed 2328 mice. J Immunol 171(3):1564-71. [PubMed: 12874250]  [MGI Ref ID J:120665]

Kaplan MH; Wurster AL; Grusby MJ. 1998. A signal transducer and activator of transcription (Stat)4-independent pathway for the development of T helper type 1 cells. J Exp Med 188(6):1191-6. [PubMed: 9743537]  [MGI Ref ID J:50032]

Kataoka TR; Nishizawa Y. 2008. Stat4 suppresses the proliferation of connective tissue-type mast cells. Lab Invest 88(8):856-64. [PubMed: 18521064]  [MGI Ref ID J:138166]

Kim SH; Gunst KV; Sarvetnick N. 2006. STAT4/6-dependent differential regulation of chemokine receptors. Clin Immunol 118(2-3):250-7. [PubMed: 16413227]  [MGI Ref ID J:107223]

Kishimoto K; Dong VM; Issazadeh S; Fedoseyeva EV; Waaga AM; Yamada A; Sho M; Benichou G; Auchincloss H Jr; Grusby MJ; Khoury SJ; Sayegh MH. 2000. The role of CD154-CD40 versus CD28-B7 costimulatory pathways in regulating allogeneic Th1 and Th2 responses in vivo. J Clin Invest 106(1):63-72. [PubMed: 10880049]  [MGI Ref ID J:63156]

Land KJ; Gudapati P; Kaplan MH; Seetharamaiah GS. 2006. Differential requirement of signal transducer and activator of transcription-4 (Stat4) and Stat6 in a thyrotropin receptor-289-adenovirus-induced model of Graves' hyperthyroidism. Endocrinology 147(1):111-9. [PubMed: 16195404]  [MGI Ref ID J:129448]

Martin SF; Dudda JC; Bachtanian E; Lembo A; Liller S; Durr C; Heimesaat MM; Bereswill S; Fejer G; Vassileva R; Jakob T; Freudenberg N; Termeer CC; Johner C; Galanos C; Freudenberg MA. 2008. Toll-like receptor and IL-12 signaling control susceptibility to contact hypersensitivity. J Exp Med 205(9):2151-62. [PubMed: 18725520]  [MGI Ref ID J:138813]

Matsukawa A; Kaplan MH; Hogaboam CM; Lukacs NW; Kunkel SL. 2001. Pivotal role of signal transducer and activator of transcription (stat)4 and stat6 in the innate immune response during sepsis. J Exp Med 193(6):679-88. [PubMed: 11257135]  [MGI Ref ID J:68143]

Miyagi T; Gil MP; Wang X; Louten J; Chu WM; Biron CA. 2007. High basal STAT4 balanced by STAT1 induction to control type 1 interferon effects in natural killer cells. J Exp Med 204(10):2383-96. [PubMed: 17846149]  [MGI Ref ID J:126055]

Mo C; Chearwae W; O'Malley JT; Adams SM; Kanakasabai S; Walline CC; Stritesky GL; Good SR; Perumal NB; Kaplan MH; Bright JJ. 2008. Stat4 isoforms differentially regulate inflammation and demyelination in experimental allergic encephalomyelitis. J Immunol 181(8):5681-90. [PubMed: 18832727]  [MGI Ref ID J:140753]

Morris SC; Orekhova T; Meadows MJ; Heidorn SM; Yang J; Finkelman FD. 2006. IL-4 induces in vivo production of IFN-gamma by NK and NKT cells. J Immunol 176(9):5299-305. [PubMed: 16621996]  [MGI Ref ID J:131660]

Najafian N; Chitnis T; Salama AD; Zhu B; Benou C; Yuan X; Clarkson MR; Sayegh MH; Khoury SJ. 2003. Regulatory functions of CD8+CD28- T cells in an autoimmune disease model. J Clin Invest 112(7):1037-48. [PubMed: 14523041]  [MGI Ref ID J:85805]

Nandakumar KS; Holmdahl R. 2006. Arthritis induced with cartilage-specific antibodiesis IL-4-dependent. Eur J Immunol 36(6):1608-18. [PubMed: 16688680]  [MGI Ref ID J:115066]

Niesner U; Albrecht I; Janke M; Doebis C; Loddenkemper C; Lexberg MH; Eulenburg K; Kreher S; Koeck J; Baumgrass R; Bonhagen K; Kamradt T; Enghard P; Humrich JY; Rutz S; Schulze-Topphoff U; Aktas O; Bartfeld S; Radbruch H; Hegazy AN; Lohning M; Baumgart DC; Duchmann R; Rudwaleit M; Haupl T; Gitelman I; Krenn V; Gruen J; Sieper J; Zeitz M; Wiedenmann B; Zipp F; Hamann A; Janitz M; Scheffold A; Burmester GR; Chang HD; Radbruch A. 2008. Autoregulation of Th1-mediated inflammation by twist1. J Exp Med 205(8):1889-901. [PubMed: 18663125]  [MGI Ref ID J:139533]

Nikolic B; Lee S; Bronson RT; Grusby MJ; Sykes M. 2000. Th1 and Th2 mediate acute graft-versus-host disease, each with distinct end-organ targets. J Clin Invest 105(9):1289-98. [PubMed: 10792004]  [MGI Ref ID J:62114]

Nishikomori R; Usui T; Wu CY; Morinobu A; O'Shea JJ; Strober W. 2002. Activated STAT4 has an essential role in Th1 differentiation and proliferation that is independent of its role in the maintenance of IL-12Rbeta2 chain expression and signaling. J Immunol 169(8):4388-98. [PubMed: 12370372]  [MGI Ref ID J:79543]

Nurieva RI; Chung Y; Hwang D; Yang XO; Kang HS; Ma L; Wang YH; Watowich SS; Jetten AM; Tian Q; Dong C. 2008. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity 29(1):138-49. [PubMed: 18599325]  [MGI Ref ID J:137869]

O'Malley JT; Eri RD; Stritesky GL; Mathur AN; Chang HC; Hogenesch H; Srinivasan M; Kaplan MH. 2008. STAT4 isoforms differentially regulate Th1 cytokine production and the severity of inflammatory bowel disease. J Immunol 181(7):5062-70. [PubMed: 18802110]  [MGI Ref ID J:142733]

Ostrand-Rosenberg S; Grusby MJ; Clements VK. 2000. Cutting edge: STAT6-deficient mice have enhanced tumor immunity to primary and metastatic mammary carcinoma J Immunol 165(11):6015-9. [PubMed: 11086031]  [MGI Ref ID J:65894]

Owaki T; Asakawa M; Kamiya S; Takeda K; Fukai F; Mizuguchi J; Yoshimoto T. 2006. IL-27 suppresses CD28-mediated [correction of medicated] IL-2 production through suppressor of cytokine signaling 3. J Immunol 176(5):2773-80. [PubMed: 16493033]  [MGI Ref ID J:129424]

Owaki T; Asakawa M; Morishima N; Hata K; Fukai F; Matsui M; Mizuguchi J; Yoshimoto T. 2005. A role for IL-27 in early regulation of Th1 differentiation. J Immunol 175(4):2191-200. [PubMed: 16081786]  [MGI Ref ID J:107503]

Palmqvist P; Lundberg P; Persson E; Johansson A; Lundgren I; Lie A; Conaway HH; Lerner UH. 2006. Inhibition of hormone and cytokine-stimulated osteoclastogenesis and bone resorption by interleukin-4 and interleukin-13 is associated with increased osteoprotegerin and decreased RANKL and RANK in a STAT6-dependent pathway. J Biol Chem 281(5):2414-29. [PubMed: 16251181]  [MGI Ref ID J:107499]

Pasare C; Medzhitov R. 2004. Toll-dependent control mechanisms of CD4 T cell activation. Immunity 21(5):733-41. [PubMed: 15539158]  [MGI Ref ID J:93824]

Peck-Palmer OM; Unsinger J; Chang KC; Davis CG; McDunn JE; Hotchkiss RS. 2008. Deletion of MyD88 markedly attenuates sepsis-induced T and B lymphocyte apoptosis but worsens survival. J Leukoc Biol 83(4):1009-18. [PubMed: 18211965]  [MGI Ref ID J:134048]

Rocha FJ; Schleicher U; Mattner J; Alber G; Bogdan C. 2007. Cytokines, signaling pathways, and effector molecules required for the control of Leishmania (Viannia) braziliensis in mice. Infect Immun 75(8):3823-32. [PubMed: 17517868]  [MGI Ref ID J:123377]

Rodriguez M; Zoecklein L; Gamez JD; Pavelko KD; Papke LM; Nakane S; Howe C; Radhakrishnan S; Hansen MJ; David CS; Warrington AE; Pease LR. 2006. STAT4- and STAT6-signaling molecules in a murine model of multiple sclerosis. FASEB J 20(2):343-5. [PubMed: 16352646]  [MGI Ref ID J:105734]

Rodriguez-Galan MC; Bream JH; Farr A; Young HA. 2005. Synergistic effect of IL-2, IL-12, and IL-18 on thymocyte apoptosis and Th1/Th2 cytokine expression. J Immunol 174(5):2796-804. [PubMed: 15728489]  [MGI Ref ID J:97710]

Ruby CE; Montler R; Zheng R; Shu S; Weinberg AD. 2008. IL-12 is required for anti-OX40-mediated CD4 T cell survival. J Immunol 180(4):2140-8. [PubMed: 18250420]  [MGI Ref ID J:131920]

Sanchez-Guajardo V; Borghans JA; Marquez ME; Garcia S; Freitas AA. 2005. Different competitive capacities of Stat4- and Stat6-deficient CD4+ T cells during lymphophenia-driven proliferation. J Immunol 174(3):1178-87. [PubMed: 15661871]  [MGI Ref ID J:96425]

Shaw MH; Freeman GJ; Scott MF; Fox BA; Bzik DJ; Belkaid Y; Yap GS. 2006. Tyk2 negatively regulates adaptive Th1 immunity by mediating IL-10 signaling and promoting IFN-gamma-dependent IL-10 reactivation. J Immunol 176(12):7263-71. [PubMed: 16751369]  [MGI Ref ID J:132232]

Shen R; Kaplan MH. 2002. The homeostasis but not the differentiation of T cells is regulated by p27(Kip1). J Immunol 169(2):714-21. [PubMed: 12097373]  [MGI Ref ID J:123837]

Shen XD; Ke B; Zhai Y; Gao F; Anselmo D; Lassman CR; Busuttil RW; Kupiec-Weglinski JW. 2003. Stat4 and Stat6 signaling in hepatic ischemia/reperfusion injury in mice: HO-1 dependence of Stat4 disruption-mediated cytoprotection. Hepatology 37(2):296-303. [PubMed: 12540779]  [MGI Ref ID J:105818]

Shi HN; Grusby MJ; Nagler-Anderson C. 1999. Orally induced peripheral nonresponsiveness is maintained in the absence of functional Th1 or Th2 cells. J Immunol 162(9):5143-8. [PubMed: 10227985]  [MGI Ref ID J:112262]

Sho M; Yamada A; Najafian N; Salama AD; Harada H; Sandner SE; Sanchez-Fueyo A; Zheng XX; Strom TB; Sayegh MH. 2002. Physiological mechanisms of regulating alloimmunity: cytokines, CTLA-4, CD25+ cells, and the alloreactive T cell clone size. J Immunol 169(7):3744-51. [PubMed: 12244168]  [MGI Ref ID J:120408]

Simovic MO; Ballard BR; Gray KD; Stain SC. 2007. The STAT4 and STAT6 pathways in pancreatitis-associated lung injury. J Surg Res 137(1):10-5. [PubMed: 17109890]  [MGI Ref ID J:128064]

Singh RR; Saxena V; Zang S; Li L; Finkelman FD; Witte DP; Jacob CO. 2003. Differential contribution of IL-4 and STAT6 vs STAT4 to the development of lupus nephritis. J Immunol 170(9):4818-25. [PubMed: 12707364]  [MGI Ref ID J:123824]

Smeltz RB; Chen J; Shevach EM. 2005. Transforming growth factor-beta1 enhances the interferon-gamma-dependent, interleukin-12-independent pathway of T helper 1 cell differentiation. Immunology 114(4):484-92. [PubMed: 15804285]  [MGI Ref ID J:97437]

Sugawara I; Yamada H; Mizuno S. 2003. Relative importance of STAT4 in murine tuberculosis. J Med Microbiol 52(Pt 1):29-34. [PubMed: 12488562]  [MGI Ref ID J:106129]

Syrbe U; Hoffmann U; Schlawe K; Liesenfeld O; Erb K; Hamann A. 2006. Microenvironment-dependent requirement of STAT4 for the induction of P-selectin ligands and effector cytokines on CD4+ T cells in healthy and parasite-infected mice. J Immunol 177(11):7673-9. [PubMed: 17114437]  [MGI Ref ID J:140597]

Tarleton RL; Grusby MJ; Zhang L. 2000. Increased susceptibility of Stat4-deficient and enhanced resistance in Stat6-deficient mice to infection with Trypanosoma cruzi. J Immunol 165(3):1520-5. [PubMed: 10903759]  [MGI Ref ID J:120438]

Tekkanat KK; Maassab H; Berlin AA; Lincoln PM; Evanoff HL; Kaplan MH; Lukacs NW. 2001. Role of interleukin-12 and stat-4 in the regulation of airway inflammation and hyperreactivity in respiratory syncytial virus infection. Am J Pathol 159(2):631-8. [PubMed: 11485921]  [MGI Ref ID J:70865]

Ueno T; Habicht A; Clarkson MR; Albin MJ; Yamaura K; Boenisch O; Popoola J; Wang Y; Yagita H; Akiba H; Ansari MJ; Yang J; Turka LA; Rothstein DM; Padera RF; Najafian N; Sayegh MH. 2008. The emerging role of T cell Ig mucin 1 in alloimmune responses in an experimental mouse transplant model. J Clin Invest 118(2):742-51. [PubMed: 18172549]  [MGI Ref ID J:131045]

Underhill GH; Zisoulis DG; Kolli KP; Ellies LG; Marth JD; Kansas GS. 2005. A crucial role for T-bet in selectin ligand expression in T helper 1 (Th1) cells. Blood 106(12):3867-73. [PubMed: 16099875]  [MGI Ref ID J:124068]

Villarino AV; Stumhofer JS; Saris CJ; Kastelein RA; de Sauvage FJ; Hunter CA. 2006. IL-27 limits IL-2 production during Th1 differentiation. J Immunol 176(1):237-47. [PubMed: 16365415]  [MGI Ref ID J:126267]

Villarino AV; Tato CM; Stumhofer JS; Yao Z; Cui YK; Hennighausen L; O'Shea JJ; Hunter CA. 2007. Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals. J Exp Med 204(1):65-71. [PubMed: 17227909]  [MGI Ref ID J:125293]

Wang W; Ostlie NS; Conti-Fine BM; Milani M. 2004. The susceptibility to experimental myasthenia gravis of STAT6-/- and STAT4-/- BALB/c mice suggests a pathogenic role of Th1 cells. J Immunol 172(1):97-103. [PubMed: 14688314]  [MGI Ref ID J:87570]

White SJ; Underhill GH; Kaplan MH; Kansas GS. 2001. Cutting edge: differential requirements for Stat4 in expression of glycosyltransferases responsible for selectin ligand formation in Th1 cells. J Immunol 167(2):628-31. [PubMed: 11441063]  [MGI Ref ID J:120508]

Wilson DC; Matthews S; Yap GS. 2008. IL-12 Signaling Drives CD8+ T Cell IFN-{gamma} Production and Differentiation of KLRG1+ Effector Subpopulations during Toxoplasma gondii Infection. J Immunol 180(9):5935-45. [PubMed: 18424713]  [MGI Ref ID J:134314]

Xu Z; Duan B; Croker BP; Morel L. 2006. STAT4 deficiency reduces autoantibody production and glomerulonephritis in a mouse model of lupus. Clin Immunol 120(2):189-98. [PubMed: 16713741]  [MGI Ref ID J:113234]

Yang Z; Chen M; Ellett JD; Fialkow LB; Carter JD; McDuffie M; Nadler JL. 2004. Autoimmune diabetes is blocked in Stat4-deficient mice. J Autoimmun 22(3):191-200. [PubMed: 15041039]  [MGI Ref ID J:90600]

Yap GS; Ortmann R; Shevach E; Sher A. 2001. A heritable defect in IL-12 signaling in B10.Q/J mice. II. Effect on acute resistance to Toxoplasma gondii and rescue by IL-18 treatment. J Immunol 166(9):5720-5. [PubMed: 11313414]  [MGI Ref ID J:120304]

Yokota N; Burne-Taney M; Racusen L; Rabb H. 2003. Contrasting roles for STAT4 and STAT6 signal transduction pathways in murine renal ischemia-reperfusion injury. Am J Physiol Renal Physiol 285(2):F319-25. [PubMed: 12709397]  [MGI Ref ID J:84825]

Yu Q; Chang HC; Ahyi AN; Kaplan MH. 2008. Transcription factor-dependent chromatin remodeling of Il18r1 during Th1 and Th2 differentiation. J Immunol 181(5):3346-52. [PubMed: 18714006]  [MGI Ref ID J:138949]

Zhang F; Boothby M. 2006. T helper type 1-specific Brg1 recruitment and remodeling of nucleosomes positioned at the IFN-gamma promoter are Stat4 dependent. J Exp Med 203(6):1493-505. [PubMed: 16717115]  [MGI Ref ID J:124379]

Zhang Y; Kirken RA; Furian L; Janczewska S; Qu X; Hancock WW; Wang M; Tejpal N; Kerman R; Kahan BD; Stepkowski SM. 2006. Allograft rejection requires STAT5a/b-regulated antiapoptotic activity in T cells but not B cells. J Immunol 176(1):128-37. [PubMed: 16365403]  [MGI Ref ID J:126249]

Zhou P; Szot GL; Guo Z; Kim O; He G; Wang J; Grusby MJ; Newell KA; Thistlethwaite JR; Bluestone JA; Alegre ML. 2000. Role of STAT4 and STAT6 signaling in allograft rejection and CTLA4-Ig-mediated tolerance. J Immunol 165(10):5580-7. [PubMed: 11067913]  [MGI Ref ID J:119580]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Mating SystemHomozygote x Homozygote         (Female x Male)
Diet Information LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Weeks of AgePrice (US dollars $)GenderGenotypes Provided
Individual Mouse Price $82.10Female or MaleHomozygous for Stat4tm1Gru
Pairs /Price (US dollars $)Pair Genotype
$164.20Homozygous for Stat4tm1Gru x Homozygous for Stat4tm1Gru

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Weeks of AgePrice (US dollars $)GenderGenotypes Provided
Individual Mouse Price $106.80Female or MaleHomozygous for Stat4tm1Gru
Pairs /Price (US dollars $)Pair Genotype
$213.50Homozygous for Stat4tm1Gru x Homozygous for Stat4tm1Gru

Additional Supply Details

Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes

Control Information

  Control
   000651 BALB/cJ
 
  Considerations for Choosing Controls
  USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
  International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions


See Terms of Use


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.
Ordering and Purchasing Information

      Purchasing Information
      JAX® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:207-288-6470
fax:207-288-6655

JAX® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

No Warranty

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

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

No Liability

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

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

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

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


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