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 System Homozygote x Homozygote         (Female x Male)   01-MAR-06 Species laboratory mouse Background Strain BALB/c Donor Strain 129S2 via D3 ES cell line Generation N10F30 (19-MAY-11) Generation Definitions   Donating Investigator Dr. Michael J. Grusby,   Harvard Medical School

View larger image

Appearance
albino
Related Genotype: A/A Tyrp1^b/Tyrp1^b Tyr^c/Tyr^c

Description
Mice homozygous for the Stat4^tm1Gru 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.

Development
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.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Stat4^tm1Gru allele

003750	C.129S2-Stat4tm1Gru Stat6tm1Gru/J
004671	NOD.129S2-Stat4tm1Gru/JbsJ

View Strains carrying   Stat4^tm1Gru     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Diabetes Mellitus, Insulin-Dependent; IDDM

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Systemic Lupus Erythematosus, Susceptibility to, 11; SLEB11   (STAT4)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Stat4^tm1Gru/Stat4^tm1Gru

        C.129S2-Stat4^tm1Gru

• immune system phenotype
• abnormal CD4-positive T cell differentiation
  • wild-type CD4⁺ T cells polarized under Th17 conditions can be converted to a Th1-like cells (i.e. they express IFN-gamma) by culturing with IL-12   (MGI Ref ID J:143729)
  • mutant polarized Th17 CD4⁺ T cells fail to convert to the Th1-like state in the presence of IL-12   (MGI Ref ID J:143729)
• decreased circulating interferon-gamma level
  • 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   (MGI Ref ID J:90600)
• decreased circulating interleukin-2 level
  • 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   (MGI Ref ID J:90600)
• homeostasis/metabolism phenotype
• decreased circulating interferon-gamma level
  • 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   (MGI Ref ID J:90600)
• decreased circulating interleukin-2 level
  • 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   (MGI Ref ID J:90600)
• hematopoietic system phenotype
• abnormal CD4-positive T cell differentiation
  • wild-type CD4⁺ T cells polarized under Th17 conditions can be converted to a Th1-like cells (i.e. they express IFN-gamma) by culturing with IL-12   (MGI Ref ID J:143729)
  • mutant polarized Th17 CD4⁺ T cells fail to convert to the Th1-like state in the presence of IL-12   (MGI Ref ID J:143729)
• cellular phenotype
• abnormal CD4-positive T cell differentiation
  • wild-type CD4⁺ T cells polarized under Th17 conditions can be converted to a Th1-like cells (i.e. they express IFN-gamma) by culturing with IL-12   (MGI Ref ID J:143729)
  • mutant polarized Th17 CD4⁺ T cells fail to convert to the Th1-like state in the presence of IL-12   (MGI Ref ID J:143729)
• renal/urinary system phenotype
• abnormal kidney physiology
  • onset of ischemia effects is delayed   (MGI Ref ID J:84825)

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

Stat4^tm1Gru/Stat4^tm1Gru

        involves: 129S2/SvPas * BALB/c

• mortality/aging
• increased susceptibility to bacterial infection induced morbidity/mortality
  • Salmonella-infected mice exhibit increased mortality compared with similarly treated heterozygous or wild-type mice   (MGI Ref ID J:163843)
• immune system phenotype
• abnormal lymphocyte physiology   (MGI Ref ID J:34059)
• • abnormal NK cell physiology
    • 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)   (MGI Ref ID J:34059)
  • abnormal T cell proliferation
    • activated T lymphocytes stimulated with IL-12 for 48 hours do not proliferate, whereas activated lymphocytes from control mice exhibit dose-dependent proliferation   (MGI Ref ID J:34059)
  • abnormal T-helper 1 physiology
    • 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   (MGI Ref ID J:34059)
    • significant levels of Th2 cytokines IL-5 and IL-10 are detected in supernatants from these cultured lymphocytes   (MGI Ref ID J:34059)
  • abnormal T-helper 2 physiology
    • lymphocytes cultured in the presence of IL-4 and IFNG produce significantly higher levels of Th2 cytokines than control cells   (MGI Ref ID J:34059)
• decreased circulating interferon-gamma level
  • in Salmonella-infected mice   (MGI Ref ID J:163843)
• decreased interferon-gamma secretion
  • 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   (MGI Ref ID J:34059)
• increased susceptibility to bacterial infection
  • Salmonella-infected mice exhibit increased mortality, increased organ bacterial burden, and decreased IFN-gamma levels compared with similarly treated heterozygous or wild-type mice   (MGI Ref ID J:163843)
• • increased susceptibility to bacterial infection induced morbidity/mortality
    • Salmonella-infected mice exhibit increased mortality compared with similarly treated heterozygous or wild-type mice   (MGI Ref ID J:163843)
• hematopoietic system phenotype
• abnormal T cell proliferation
  • activated T lymphocytes stimulated with IL-12 for 48 hours do not proliferate, whereas activated lymphocytes from control mice exhibit dose-dependent proliferation   (MGI Ref ID J:34059)
• homeostasis/metabolism phenotype
• decreased circulating interferon-gamma level
  • in Salmonella-infected mice   (MGI Ref ID J:163843)
• cellular phenotype
• abnormal T cell proliferation
  • activated T lymphocytes stimulated with IL-12 for 48 hours do not proliferate, whereas activated lymphocytes from control mice exhibit dose-dependent proliferation   (MGI Ref ID J:34059)

Stat4^tm1Gru/Stat4^tm1Gru

        involves: 129S2/SvPas

• immune system phenotype
• abnormal cytokine secretion
  • T cells from mice immunized with keyhole limpet hemocyanin (KLH) in CFA (conjugated Freund's adjuvant) produce less IL-4 and interferon gamma than wild-type in response to KLH restimulation; IL-17a levels are comparable to controls   (MGI Ref ID J:112600)

View Research Applications

Research Applications

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

Stat4^tm1Gru related

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
Intracellular Signaling Molecules

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Stat4tm1Gru
Allele Name		targeted mutation 1, Michael J Grusby
Allele Type		Targeted (knock-out)
Common Name(s)		Stat4-;
Mutation Made By		Dr. Michael Grusby,   Harvard Medical School
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/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

Stat4^tm1Gru, Melt Curve Analysis
Stat4^tm1Gru, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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]

Stat4^tm1Gru 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]

Allen SJ; Mott KR; Ghiasi H. 2010. Involvement of STAT4 in IgG subtype switching and ocular HSV-1 replication in mice. Mol Vis 16:98-104. [PubMed: 20104254]  [MGI Ref ID J:161827]

Anderson AC; Lord GM; Dardalhon V; Lee DH; Sabatos-Peyton CA; Glimcher LH; Kuchroo VK. 2010. T-bet, a Th1 transcription factor regulates the expression of Tim-3. Eur J Immunol 40(3):859-66. [PubMed: 20049876]  [MGI Ref ID J:157872]

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]

Balasubramani A; Shibata Y; Crawford GE; Baldwin AS; Hatton RD; Weaver CT. 2010. Modular utilization of distal cis-regulatory elements controls Ifng gene expression in T cells activated by distinct stimuli. Immunity 33(1):35-47. [PubMed: 20643337]  [MGI Ref ID J:162632]

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]

Bell BD; Kitajima M; Larson RP; Stoklasek TA; Dang K; Sakamoto K; Wagner KU; Reizis B; Hennighausen L; Ziegler SF. 2013. The transcription factor STAT5 is critical in dendritic cells for the development of TH2 but not TH1 responses. Nat Immunol 14(4):364-71. [PubMed: 23435120]  [MGI Ref ID J:194747]

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]

Casey KA; Mescher MF. 2007. IL-21 promotes differentiation of naive CD8 T cells to a unique effector phenotype. J Immunol 178(12):7640-8. [PubMed: 17548600]  [MGI Ref ID J:148589]

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]

Ciric B; El-behi M; Cabrera R; Zhang GX; Rostami A. 2009. IL-23 drives pathogenic IL-17-producing CD8+ T cells. J Immunol 182(9):5296-305. [PubMed: 19380776]  [MGI Ref ID J:150310]

Collins PL; Chang S; Henderson M; Soutto M; Davis GM; McLoed AG; Townsend MJ; Glimcher LH; Mortlock DP; Aune TM. 2010. Distal regions of the human IFNG locus direct cell type-specific expression. J Immunol 185(3):1492-501. [PubMed: 20574006]  [MGI Ref ID J:162475]

Collison LW; Delgoffe GM; Guy CS; Vignali KM; Chaturvedi V; Fairweather D; Satoskar AR; Garcia KC; Hunter CA; Drake CG; Murray PJ; Vignali DA. 2012. The composition and signaling of the IL-35 receptor are unconventional. Nat Immunol 13(3):290-9. [PubMed: 22306691]  [MGI Ref ID J:181328]

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]

Duhen R; Glatigny S; Arbelaez CA; Blair TC; Oukka M; Bettelli E. 2013. Cutting Edge: The Pathogenicity of IFN-gamma-Producing Th17 Cells Is Independent of T-bet. J Immunol 190(9):4478-82. [PubMed: 23543757]  [MGI Ref ID J:195506]

Eddahri F; Denanglaire S; Bureau F; Spolski R; Leonard WJ; Leo O; Andris F. 2009. Interleukin-6/STAT3 signaling regulates the ability of naive T cells to acquire B-cell help capacities. Blood 113(11):2426-33. [PubMed: 19020307]  [MGI Ref ID J:146334]

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]

Gil MP; Ploquin MJ; Watford WT; Lee SH; Kim K; Wang X; Kanno Y; O'Shea JJ; Biron CA. 2012. Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function. Blood 120(18):3718-28. [PubMed: 22968462]  [MGI Ref ID J:191417]

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]

Haapakoski R; Karisola P; Fyhrquist N; Savinko T; Wolff H; Turjanmaa K; Palosuo T; Reunala T; Lauerma A; Alenius H. 2011. Intradermal cytosine-phosphate-guanosine treatment reduces lung inflammation but induces IFN-gamma-mediated airway hyperreactivity in a murine model of natural rubber latex allergy. Am J Respir Cell Mol Biol 44(5):639-47. [PubMed: 20581096]  [MGI Ref ID J:183350]

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]

Hildner KM; Schirmacher P; Atreya I; Dittmayer M; Bartsch B; Galle PR; Wirtz S; Neurath MF. 2007. Targeting of the transcription factor STAT4 by antisense phosphorothioate oligonucleotides suppresses collagen-induced arthritis. J Immunol 178(6):3427-36. [PubMed: 17339437]  [MGI Ref ID J:144293]

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]

Ishii M; Wen H; Corsa CA; Liu T; Coelho AL; Allen RM; Carson WF 4th; Cavassani KA; Li X; Lukacs NW; Hogaboam CM; Dou Y; Kunkel SL. 2009. Epigenetic regulation of the alternatively activated macrophage phenotype. Blood 114(15):3244-54. [PubMed: 19567879]  [MGI Ref ID J:153569]

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]

Kim YK; Oh SY; Jeon SG; Park HW; Lee SY; Chun EY; Bang B; Lee HS; Oh MH; Kim YS; Kim JH; Gho YS; Cho SH; Min KU; Kim YY; Zhu Z. 2007. Airway exposure levels of lipopolysaccharide determine type 1 versus type 2 experimental asthma. J Immunol 178(8):5375-82. [PubMed: 17404323]  [MGI Ref ID J:145264]

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]

Klose CS; Kiss EA; Schwierzeck V; Ebert K; Hoyler T; d'Hargues Y; Goppert N; Croxford AL; Waisman A; Tanriver Y; Diefenbach A. 2013. A T-bet gradient controls the fate and function of CCR6-RORgammat+ innate lymphoid cells. Nature 494(7436):261-5. [PubMed: 23334414]  [MGI Ref ID J:194555]

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]

Lee CG; Kwon HK; Sahoo A; Hwang W; So JS; Hwang JS; Chae CS; Kim GC; Kim JE; So HS; Hwang ES; Grenningloh R; Ho IC; Im SH. 2012. Interaction of Ets-1 with HDAC1 Represses IL-10 Expression in Th1 Cells. J Immunol 188(5):2244-53. [PubMed: 22266280]  [MGI Ref ID J:181289]

Lee SH; Fragoso MF; Biron CA. 2012. Cutting edge: a novel mechanism bridging innate and adaptive immunity: IL-12 induction of CD25 to form high-affinity IL-2 receptors on NK cells. J Immunol 189(6):2712-6. [PubMed: 22888135]  [MGI Ref ID J:189815]

Lee YK; Turner H; Maynard CL; Oliver JR; Chen D; Elson CO; Weaver CT. 2009. Late developmental plasticity in the T helper 17 lineage. Immunity 30(1):92-107. [PubMed: 19119024]  [MGI Ref ID J:143729]

Li Q; Iuchi T; Jure-Kunkel MN; Chang AE. 2007. Adjuvant effect of anti-4-1BB mAb administration in adoptive T cell therapy of cancer. Int J Biol Sci 3(7):455-62. [PubMed: 18071585]  [MGI Ref ID J:161109]

Longman RS; Braun D; Pellegrini S; Rice CM; Darnell RB; Albert ML. 2007. Dendritic-cell maturation alters intracellular signaling networks, enabling differential effects of IFN-alpha/beta on antigen cross-presentation. Blood 109(3):1113-22. [PubMed: 17018853]  [MGI Ref ID J:144394]

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]

Mathur AN; Chang HC; Zisoulis DG; Stritesky GL; Yu Q; O'Malley JT; Kapur R; Levy DE; Kansas GS; Kaplan MH. 2007. Stat3 and Stat4 direct development of IL-17-secreting Th cells. J Immunol 178(8):4901-7. [PubMed: 17404271]  [MGI Ref ID J:145196]

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]

Menke J; Bork T; Kutska B; Byrne KT; Blanfeld M; Relle M; Kelley VR; Schwarting A. 2011. Targeting transcription factor Stat4 uncovers a role for interleukin-18 in the pathogenesis of severe lupus nephritis in mice. Kidney Int 79(4):452-63. [PubMed: 20980973]  [MGI Ref ID J:186884]

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]

Mukasa R; Balasubramani A; Lee YK; Whitley SK; Weaver BT; Shibata Y; Crawford GE; Hatton RD; Weaver CT. 2010. Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage. Immunity 32(5):616-27. [PubMed: 20471290]  [MGI Ref ID J:160694]

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]

Nakayamada S; Kanno Y; Takahashi H; Jankovic D; Lu KT; Johnson TA; Sun HW; Vahedi G; Hakim O; Handon R; Schwartzberg PL; Hager GL; O'Shea JJ. 2011. Early Th1 Cell Differentiation Is Marked by a Tfh Cell-like Transition. Immunity 35(6):919-31. [PubMed: 22195747]  [MGI Ref ID J:179278]

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]

O'Malley JT; Sehra S; Thieu VT; Yu Q; Chang HC; Stritesky GL; Nguyen ET; Mathur AN; Levy DE; Kaplan MH. 2009. Signal transducer and activator of transcription 4 limits the development of adaptive regulatory T cells. Immunology 127(4):587-95. [PubMed: 19604309]  [MGI Ref ID J:155987]

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]

Park H; Li Z; Yang XO; Chang SH; Nurieva R; Wang YH; Wang Y; Hood L; Zhu Z; Tian Q; Dong C. 2005. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6(11):1133-41. [PubMed: 16200068]  [MGI Ref ID J:112600]

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]

Pham D; Vincentz JW; Firulli AB; Kaplan MH. 2012. Twist1 regulates Ifng expression in Th1 cells by interfering with Runx3 function. J Immunol 189(2):832-40. [PubMed: 22685315]  [MGI Ref ID J:189552]

Raifer H; Mahiny AJ; Bollig N; Petermann F; Hellhund A; Kellner K; Guralnik A; Reinhard K; Bothur E; Huber M; Bauer S; Lohning M; Kiss EA; Ganal SC; Diefenbach A; Korn T; Lohoff M. 2012. Unlike alphabeta T cells, gammadelta T cells, LTi cells and NKT cells do not require IRF4 for the production of IL-17A and IL-22. Eur J Immunol 42(12):3189-201. [PubMed: 22961652]  [MGI Ref ID J:190537]

Ranatunga D; Hedrich CM; Wang F; McVicar DW; Nowak N; Joshi T; Feigenbaum L; Grant LR; Stager S; Bream JH. 2009. A human IL10 BAC transgene reveals tissue-specific control of IL-10 expression and alters disease outcome. Proc Natl Acad Sci U S A 106(40):17123-8. [PubMed: 19805095]  [MGI Ref ID J:153695]

Richer E; Prendergast C; Zhang DE; Qureshi ST; Vidal SM; Malo D. 2010. N-ethyl-N-nitrosourea-induced mutation in ubiquitin-specific peptidase 18 causes hyperactivation of IFN-alphabeta signaling and suppresses STAT4-induced IFN-gamma production, resulting in increased susceptibility to Salmonella Typhimurium. J Immunol 185(6):3593-601. [PubMed: 20693420]  [MGI Ref ID J:163843]

Riella LV; Ueno T; Batal I; De Serres SA; Bassil R; Elyaman W; Yagita H; Medina-Pestana JO; Chandraker A; Najafian N. 2011. Blockade of Notch ligand Delta1 promotes allograft survival by inhibiting alloreactive Th1 cells and cytotoxic T cell generation. J Immunol 187(9):4629-38. [PubMed: 21949024]  [MGI Ref ID J:179438]

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]

Sanchez-Guajardo V; Tanchot C; O'Malley JT; Kaplan MH; Garcia S; Freitas AA. 2007. Agonist-driven development of CD4+CD25+Foxp3+ regulatory T cells requires a second signal mediated by Stat6. J Immunol 178(12):7550-6. [PubMed: 17548589]  [MGI Ref ID J:148595]

Schilte C; Couderc T; Chretien F; Sourisseau M; Gangneux N; Guivel-Benhassine F; Kraxner A; Tschopp J; Higgs S; Michault A; Arenzana-Seisdedos F; Colonna M; Peduto L; Schwartz O; Lecuit M; Albert ML. 2010. Type I IFN controls chikungunya virus via its action on nonhematopoietic cells. J Exp Med 207(2):429-42. [PubMed: 20123960]  [MGI Ref ID J:157759]

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]

Sun JC; Madera S; Bezman NA; Beilke JN; Kaplan MH; Lanier LL. 2012. Proinflammatory cytokine signaling required for the generation of natural killer cell memory. J Exp Med 209(5):947-54. [PubMed: 22493516]  [MGI Ref ID J:185151]

Sutherland AP; Joller N; Michaud M; Liu SM; Kuchroo VK; Grusby MJ. 2013. IL-21 Promotes CD8+ CTL Activity via the Transcription Factor T-bet. J Immunol 190(8):3977-84. [PubMed: 23479229]  [MGI Ref ID J:194899]

Svensson A; Tunback P; Nordstrom I; Shestakov A; Padyukov L; Eriksson K. 2012. STAT4 regulates antiviral gamma interferon responses and recurrent disease during herpes simplex virus 2 infection. J Virol 86(17):9409-15. [PubMed: 22718836]  [MGI Ref ID J:187832]

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]

Tamachi T; Takatori H; Fujiwara M; Hirose K; Maezawa Y; Kagami S; Suto A; Watanabe N; Iwamoto I; Nakajima H. 2009. STAT6 inhibits T-bet-independent Th1 cell differentiation. Biochem Biophys Res Commun 382(4):751-5. [PubMed: 19324016]  [MGI Ref ID J:148350]

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]

Thieu VT; Yu Q; Chang HC; Yeh N; Nguyen ET; Sehra S; Kaplan MH. 2008. Signal transducer and activator of transcription 4 is required for the transcription factor T-bet to promote T helper 1 cell-fate determination. Immunity 29(5):679-90. [PubMed: 18993086]  [MGI Ref ID J:143179]

Tokumasa N; Suto A; Kagami S; Furuta S; Hirose K; Watanabe N; Saito Y; Shimoda K; Iwamoto I; Nakajima H. 2007. Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-gamma production and the induction of Th1 cell differentiation. Blood 110(2):553-60. [PubMed: 17395783]  [MGI Ref ID J:145403]

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; Artis D; Bezbradica JS; Miller O; Saris CJ; Joyce S; Hunter CA. 2008. IL-27R deficiency delays the onset of colitis and protects from helminth-induced pathology in a model of chronic IBD. Int Immunol 20(6):739-52. [PubMed: 18375937]  [MGI Ref ID J:136179]

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]

Wuthrich M; Gern B; Hung CY; Ersland K; Rocco N; Pick-Jacobs J; Galles K; Filutowicz H; Warner T; Evans M; Cole G; Klein B. 2011. Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice. J Clin Invest 121(2):554-68. [PubMed: 21206087]  [MGI Ref ID J:171835]

Xu J; Yang Y; Qiu G; Lal G; Yin N; Wu Z; Bromberg JS; Ding Y. 2011. Stat4 Is Critical for the Balance between Th17 Cells and Regulatory T Cells in Colitis. J Immunol 186(11):6597-606. [PubMed: 21525389]  [MGI Ref ID J:173182]

Xu M; Morishima N; Mizoguchi I; Chiba Y; Fujita K; Kuroda M; Iwakura Y; Cua DJ; Yasutomo K; Mizuguchi J; Yoshimoto T. 2011. Regulation of the development of acute hepatitis by IL-23 through IL-22 and IL-17 production. Eur J Immunol 41(10):2828-39. [PubMed: 21953641]  [MGI Ref ID J:176800]

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 Y; Ochando JC; Bromberg JS; Ding Y. 2007. Identification of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNgamma/Stat1 signals. Blood 110(7):2494-500. [PubMed: 17575072]  [MGI Ref ID J:147019]

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]

Yeh N; Glosson NL; Wang N; Guindon L; McKinley C; Hamada H; Li Q; Dutton RW; Shrikant P; Zhou B; Brutkiewicz RR; Blum JS; Kaplan MH. 2010. Tc17 cells are capable of mediating immunity to vaccinia virus by acquisition of a cytotoxic phenotype. J Immunol 185(4):2089-98. [PubMed: 20624947]  [MGI Ref ID J:162382]

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 S; Bernard D; Khan WI; Kaplan MH; Bramson JL; Wan Y. 2009. CD4+ T-cell-mediated anti-tumor immunity can be uncoupled from autoimmunity via the STAT4/STAT6 signaling axis. Eur J Immunol 39(5):1252-9. [PubMed: 19338001]  [MGI Ref ID J:148099]

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]

Zhong J; Yang P; Muta K; Dong R; Marrero M; Gong F; Wang CY. 2010. Loss of Jak2 selectively suppresses DC-mediated innate immune response and protects mice from lethal dose of LPS-induced septic shock. PLoS One 5(3):e9593. [PubMed: 20231889]  [MGI Ref ID J:158917]

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]

Zhu J; Jankovic D; Oler AJ; Wei G; Sharma S; Hu G; Guo L; Yagi R; Yamane H; Punkosdy G; Feigenbaum L; Zhao K; Paul WE. 2012. The Transcription Factor T-bet Is Induced by Multiple Pathways and Prevents an Endogenous Th2 Cell Program during Th1 Cell Responses. Immunity 37(4):660-73. [PubMed: 23041064]  [MGI Ref ID J:188559]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Mating System	Homozygote x Homozygote         (Female x Male)   01-MAR-06
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
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 regarding Terms of Use

Contracts Administration

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

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.

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, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, 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 JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS 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 JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON 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 JACKSON, 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 JACKSON, 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 or services by JACKSON.