Strain Name:

BALB/c-Il4tm2Nnt/J

Stock Number:

002496

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Mice homozygous for Il4tm2Nnt have significantly reduced levels of IgGl and IgE and reduced ability to produce Th2-derived cytokines. Mice are susceptible to infection by Leishmania major.

Description

Strain Information

Type Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemHomozygote x Homozygote         (Female x Male)   01-MAR-06
Specieslaboratory mouse
GenerationF?+35 (24-MAR-11)
Generation Definitions

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

Description
Mice homozygous for the Il4tm2Nnt targeted mutation are viable and fertile. T and B cell development is normal but IgGl and IgE levels and the ability of homozygous mutant mice to produce Th2-derived cytokines are significantly reduced. Susceptible to infection by Leishmania major despite deficiency in IL4.

Development
This strain was developed by Dr. Nancy Noben-Trauth and Dr. Birgit Ledermann at Sandoz Pharma Ltd. in Basel, Switzerland. A BALB/c-derived ES cell line was used.

Control Information

  Control
   000651 BALB/cJ
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of Il4     (11 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Il4tm2Nnt/Il4tm2Nnt

        BALB/c-Il4tm2Nnt/J
  • immune system phenotype
  • abnormal dendritic cell antigen presentation
    • memory CD4 T cells activated by mutant DCs from inflamed lungs secrete low levels of Th2 cytokines   (MGI Ref ID J:141937)
  • abnormal dendritic cell differentiation
    • numbers of MHCII/CD86-positive dendritic cells found in inflamed lungs are reduced by two-thirds   (MGI Ref ID J:141937)
  • decreased IgE level
    • reduced serum concentrations of IgE, however lymphocyte composition and function comparable to wild-type controls   (MGI Ref ID J:31486)
  • decreased IgG1 level
    • reduced serum concentrations of IgG1, however lymphocyte composition and function comparable to wild-type controls   (MGI Ref ID J:31486)
  • decreased interleukin-13 secretion
    • lymphocytes from mice sensitized and challenged with OVA produce less IL-13 than controls   (MGI Ref ID J:141937)
  • decreased interleukin-5 secretion
    • lymphocytes from mice sensitized and challenged with OVA produce less IL-5 than controls   (MGI Ref ID J:141937)
  • decreased susceptibility to autoimmune disorder
    • mice fail to develop blood eosinophilia after being sensitized and challenged with OVA peptide   (MGI Ref ID J:141937)
    • airway hyperresponsiveness still occurs in these mice though less mucosal cells are found in the inflamed airway   (MGI Ref ID J:141937)
  • increased interferon-gamma secretion
    • T cells from mice sensitized and challenged with OVA produce more IFN-gamma than controls   (MGI Ref ID J:141937)
  • hematopoietic system phenotype
  • abnormal dendritic cell differentiation
    • numbers of MHCII/CD86-positive dendritic cells found in inflamed lungs are reduced by two-thirds   (MGI Ref ID J:141937)
  • decreased IgE level
    • reduced serum concentrations of IgE, however lymphocyte composition and function comparable to wild-type controls   (MGI Ref ID J:31486)
  • decreased IgG1 level
    • reduced serum concentrations of IgG1, however lymphocyte composition and function comparable to wild-type controls   (MGI Ref ID J:31486)
  • craniofacial phenotype
  • abnormal alveolar process morphology
    • increase in alveolar bone loss at 30 weeks relative to mice at 6 and 16 weeks   (MGI Ref ID J:147935)
  • skeleton phenotype
  • abnormal alveolar process morphology
    • increase in alveolar bone loss at 30 weeks relative to mice at 6 and 16 weeks   (MGI Ref ID J:147935)
  • cellular phenotype
  • abnormal dendritic cell differentiation
    • numbers of MHCII/CD86-positive dendritic cells found in inflamed lungs are reduced by two-thirds   (MGI Ref ID J:141937)
  • renal/urinary system phenotype
  • abnormal kidney physiology
    • functional and histological markers for damage after ischemia are elevated   (MGI Ref ID J:84825)

Il4tm2Nnt/Il4tm2Nnt

        BALB/c-Il4tm2Nnt
  • mortality/aging
  • increased susceptibility to parasitic infection induced morbidity/mortality
    • increased mortality following acute infection with Schistosoma mansoni compared to wild-type mice   (MGI Ref ID J:60609)
  • immune system phenotype
  • abnormal splenocyte physiology
    • display a diminished type 2 cytokine response in response to soluble schistosome egg antigens compared to wild-type cells   (MGI Ref ID J:60609)
  • altered susceptibility to infection
    • T cells in the intestine have a Th1 like phenotype in S. mansoni infected mice rather than the Th2 like phenotype seen in wild-type mice   (MGI Ref ID J:60609)
    • increased susceptibility to parasitic infection
      • increase in S. mansoni infection induced liver damage measured by plasma aspartate aminotransferase levels compared to wild-type mice   (MGI Ref ID J:60609)
      • marked distension and inflammation of the ileum in S. mansoni infected mice and impaired parasite egg excretion compared to wild-type mice   (MGI Ref ID J:60609)
      • increased susceptibility to parasitic infection induced morbidity/mortality
        • increased mortality following acute infection with Schistosoma mansoni compared to wild-type mice   (MGI Ref ID J:60609)
  • ileum inflammation
    • marked distension and inflammation of the ileum in S. mansoni infected mice   (MGI Ref ID J:60609)
    • circulating levels of LPS in S. mansoni infected mice are elevated indicating impaired integrity of the gut   (MGI Ref ID J:60609)
    • T cells in the intestine have a Th1 like phenotype in S. mansoni infected mice rather than the Th2 like phenotype seen in wild-type mice   (MGI Ref ID J:60609)
  • hematopoietic system phenotype
  • abnormal splenocyte physiology
    • display a diminished type 2 cytokine response in response to soluble schistosome egg antigens compared to wild-type cells   (MGI Ref ID J:60609)
  • digestive/alimentary phenotype
  • ileum inflammation
    • marked distension and inflammation of the ileum in S. mansoni infected mice   (MGI Ref ID J:60609)
    • circulating levels of LPS in S. mansoni infected mice are elevated indicating impaired integrity of the gut   (MGI Ref ID J:60609)
    • T cells in the intestine have a Th1 like phenotype in S. mansoni infected mice rather than the Th2 like phenotype seen in wild-type mice   (MGI Ref ID J:60609)
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Research Applications
This mouse can be used to support research in many areas including:

Il4tm2Nnt related

Cancer Research
Growth Factors/Receptors/Cytokines

Immunology, Inflammation and Autoimmunity Research
Growth Factors/Receptors/Cytokines

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Il4tm2Nnt
Allele Name targeted mutation 2, Nancy Noben-Trauth
Allele Type Targeted (knock-out)
Common Name(s) IL-4-;
Mutation Made By Nancy Noben-Trauth,  
Strain of OriginBALB/cJ
ES Cell Line NameBALB/c-I
ES Cell Line StrainBALB/cJ
Gene Symbol and Name Il4, interleukin 4
Chromosome 11
Gene Common Name(s) BCGF-1; BCGF1; BSF-1; BSF1; IL-4; Il-4; Il4e12;
General Note Susceptibility to Leishmania major in BALB/c mice has been ablated by introduction of a null mutant of the Il4 gene (J:35236), but in that study the introduced mutant came from a strain 129 background, and 129 is resistant to L. major infection. In mice carrying one of Noben-Trauth's null mutants, targeted in BALB/c embryonic stem cells, the loss of Il4 expression did not remove susceptibility to infection (J:31486).
Molecular Note A neomycin resistance cassette was inserted into exon 3 of the gene. [MGI Ref ID J:36386]

Genotyping

Genotyping Information

Genotyping Protocols

Il4tm2Nnt, Separated PCR
Il4tm2Nnt, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Noben-Trauth N; Kohler G; Burki K; Ledermann B. 1996. Efficient targeting of the IL-4 gene in a BALB/c embryonic stem cell line. Transgenic Res 5(6):487-91. [PubMed: 8840532]  [MGI Ref ID J:36386]

Additional References

Czarneski J; Meyers J; Peng T; Abraham V; Mick R; Ross SR. 2001. Interleukin-4 Up-Regulates Mouse Mammary Tumor Virus Expression yet Is Not Required for In Vivo Virus Spread. J Virol 75(23):11886-90. [PubMed: 11689671]  [MGI Ref ID J:73032]

Dohi T; Fujihashi K; Kiyono H; Elson CO; McGhee JR. 2000. Mice deficient in Th1- and Th2-type cytokines develop distinct forms of hapten-induced colitis. Gastroenterology 119(3):724-33. [PubMed: 10982767]  [MGI Ref ID J:64230]

Hall LR; Berger RB; Diaconu E; Pearlman E. 2002. Onchocerca volvulus keratitis (river blindness) is exacerbated in BALB/c IL-4 gene knockout mice. Cell Immunol 216(1-2):1-5. [PubMed: 12381344]  [MGI Ref ID J:80510]

Hata H; Sakaguchi N; Yoshitomi H; Iwakura Y; Sekikawa K; Azuma Y; Kanai C; Moriizumi E; Nomura T; Nakamura T; Sakaguchi S. 2004. Distinct contribution of IL-6, TNF-alpha, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice. J Clin Invest 114(4):582-8. [PubMed: 15314695]  [MGI Ref ID J:92002]

Kodera T; McGaha TL; Phelps R; Paul WE; Bona CA. 2002. Disrupting the IL-4 gene rescues mice homozygous for the tight-skin mutation from embryonic death and diminishes TGF-beta production by fibroblasts. Proc Natl Acad Sci U S A 99(6):3800-5. [PubMed: 11891315]  [MGI Ref ID J:75471]

Kolodsick JE; Toews GB; Jakubzick C; Hogaboam C; Moore TA; McKenzie A; Wilke CA; Chrisman CJ; Moore BB. 2004. Protection from fluorescein isothiocyanate-induced fibrosis in IL-13-deficient, but not IL-4-deficient, mice results from impaired collagen synthesis by fibroblasts. J Immunol 172(7):4068-76. [PubMed: 15034018]  [MGI Ref ID J:88681]

Li X; Wang Y; Urso D; O'Rourke J; Cone RE. 2004. Thymocytes induced by antigen injection into the anterior chamber activate splenic CD8+ suppressor cells and enhance the antigen-induced production of immunoglobulin G1 antibodies. Immunology 113(1):44-56. [PubMed: 15312135]  [MGI Ref ID J:92936]

Noben-Trauth N; Kropf P; Muller I. 1996. Susceptibility to Leishmania major infection in interleukin-4-deficient mice [see comments] Science 271(5251):987-90. [PubMed: 8584936]  [MGI Ref ID J:31486]

Spencer L; Shultz L; Rajan TV. 2001. Interleukin-4 receptor-stat6 signaling in murine infections with a tissue-dwelling nematode parasite. Infect Immun 69(12):7743-52. [PubMed: 11705956]  [MGI Ref ID J:73137]

Woolard MD; Hodge LM; Jones HP; Schoeb TR; Simecka JW. 2004. The upper and lower respiratory tracts differ in their requirement of IFN-gamma and IL-4 in controlling respiratory mycoplasma infection and disease. J Immunol 172(11):6875-83. [PubMed: 15153506]  [MGI Ref ID J:90522]

Il4tm2Nnt related

Abston ED; Coronado MJ; Bucek A; Onyimba JA; Brandt JE; Frisancho JA; Kim E; Bedja D; Sung YK; Radtke AJ; Gabrielson KL; Mitzner W; Fairweather D. 2013. TLR3 deficiency induces chronic inflammatory cardiomyopathy in resistant mice following coxsackievirus B3 infection: role for IL-4. Am J Physiol Regul Integr Comp Physiol 304(4):R267-77. [PubMed: 23255589]  [MGI Ref ID J:195232]

Alayan J; Ivanovski S; Farah CS. 2007. Alveolar bone loss in T helper 1/T helper 2 cytokine-deficient mice. J Periodontal Res 42(2):97-103. [PubMed: 17305866]  [MGI Ref ID J:147935]

Alexander J; Carter KC; Al-Fasi N; Satoskar A; Brombacher F. 2000. Endogenous IL-4 is necessary for effective drug therapy against visceral leishmaniasis Eur J Immunol 30(10):2935-43. [PubMed: 11069076]  [MGI Ref ID J:65232]

Andoh A; Masuda A; Kumazawa Y; Kasajima T. 2002. Serum antibody response and nasal lymphoid tissue (NALT) structure in the absence of IL-4 or IFN-gamma. Cytokine 20(3):107-12. [PubMed: 12453468]  [MGI Ref ID J:102594]

Artis D; Humphreys NE; Bancroft AJ; Rothwell NJ; Potten CS; Grencis RK. 1999. Tumor necrosis factor alpha is a critical component of interleukin 13-mediated protective T helper cell type 2 responses during helminth infection. J Exp Med 190(7):953-62. [PubMed: 10510085]  [MGI Ref ID J:115088]

Belkaid Y; Mendez S; Lira R; Kadambi N; Milon G; Sacks D. 2000. A natural model of Leishmania major infection reveals a prolonged 'silent' phase of parasite amplification in the skin before the onset of lesion formation and immunity. J Immunol 165(2):969-77. [PubMed: 10878373]  [MGI Ref ID J:120233]

Bian K; Zhong M; Harari Y; Lai M; Weisbrodt N; Murad F. 2005. Helminth regulation of host IL-4Ralpha/Stat6 signaling: mechanism underlying NOS-2 inhibition by Trichinella spiralis. Proc Natl Acad Sci U S A 102(11):3936-41. [PubMed: 15741272]  [MGI Ref ID J:97167]

Brewer JM; Conacher M; Hunter CA; Mohrs M; Brombacher F; Alexander J. 1999. Aluminium hydroxide adjuvant initiates strong antigen-specific Th2 responses in the absence of IL-4- or IL-13-mediated signaling. J Immunol 163(12):6448-54. [PubMed: 10586035]  [MGI Ref ID J:58976]

Cao Y; Brombacher F; Tunyogi-Csapo M; Glant TT; Finnegan A. 2007. Interleukin-4 regulates proteoglycan-induced arthritis by specifically suppressing the innate immune response. Arthritis Rheum 56(3):861-70. [PubMed: 17330244]  [MGI Ref ID J:168136]

Castilow EM; Meyerholz DK; Varga SM. 2008. IL-13 is required for eosinophil entry into the lung during respiratory syncytial virus vaccine-enhanced disease. J Immunol 180(4):2376-84. [PubMed: 18250447]  [MGI Ref ID J:131994]

Chappell CP; Draves KE; Giltiay NV; Clark EA. 2012. Extrafollicular B cell activation by marginal zone dendritic cells drives T cell-dependent antibody responses. J Exp Med 209(10):1825-40. [PubMed: 22966002]  [MGI Ref ID J:191423]

Cohn L; Herrick C; Niu N; Homer R; Bottomly K. 2001. IL-4 promotes airway eosinophilia by suppressing IFN-gamma production: defining a novel role for IFN-gamma in the regulation of allergic airway inflammation. J Immunol 166(4):2760-7. [PubMed: 11160342]  [MGI Ref ID J:126916]

Dogan RN; Vasu C; Holterman MJ; Prabhakar BS. 2003. Absence of IL-4, and not suppression of the Th2 response, prevents development of experimental autoimmune Graves' disease. J Immunol 170(4):2195-204. [PubMed: 12574393]  [MGI Ref ID J:126279]

Dohi T; Fujihashi K; Kiyono H; Elson CO; McGhee JR. 2000. Mice deficient in Th1- and Th2-type cytokines develop distinct forms of hapten-induced colitis. Gastroenterology 119(3):724-33. [PubMed: 10982767]  [MGI Ref ID J:64230]

Dohi T; Fujihashi K; Rennert PD; Iwatani K; Kiyono H; McGhee JR. 1999. Hapten-induced colitis is associated with colonic patch hypertrophy and T helper cell 2-type responses. J Exp Med 189(8):1169-80. [PubMed: 10209035]  [MGI Ref ID J:119172]

Fallon PG; Richardson EJ; McKenzie GJ; McKenzie AN. 2000. Schistosome infection of transgenic mice defines distinct and contrasting pathogenic roles for IL-4 and IL-13: IL-13 is a profibrotic agent. J Immunol 164(5):2585-91. [PubMed: 10679097]  [MGI Ref ID J:60609]

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]

Fish SC; Donaldson DD; Goldman SJ; Williams CM; Kasaian MT. 2005. IgE generation and mast cell effector function in mice deficient in IL-4 and IL-13. J Immunol 174(12):7716-24. [PubMed: 15944273]  [MGI Ref ID J:100883]

Fujita K; Kobayashi M; Brutkiewicz RR; Hanafusa T; Herndon DN; Suzuki F. 2006. Role for IL-4 nonproducing NKT cells in CC-chemokine ligand 2-induced Th2 cell generation. Immunol Cell Biol 84(1):44-50. [PubMed: 16277637]  [MGI Ref ID J:105853]

Gallina G; Dolcetti L; Serafini P; De Santo C; Marigo I; Colombo MP; Basso G; Brombacher F; Borrello I; Zanovello P; Bicciato S; Bronte V. 2006. Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. J Clin Invest 116(10):2777-90. [PubMed: 17016559]  [MGI Ref ID J:114986]

Ghassabeh GH; De Baetselier P; Brys L; Noel W; Van Ginderachter JA; Meerschaut S; Beschin A; Brombacher F; Raes G. 2006. Identification of a common gene signature for type II cytokine-associated myeloid cells elicited in vivo in different pathologic conditions. Blood 108(2):575-83. [PubMed: 16556895]  [MGI Ref ID J:135755]

Gorham JD; Lin JT; Sung JL; Rudner LA; French MA. 2001. Genetic regulation of autoimmune disease: balb/c background tgf-beta1-deficient mice develop necroinflammatory ifn-gamma-dependent hepatitis. J Immunol 166(10):6413-22. [PubMed: 11342667]  [MGI Ref ID J:69346]

Hata H; Sakaguchi N; Yoshitomi H; Iwakura Y; Sekikawa K; Azuma Y; Kanai C; Moriizumi E; Nomura T; Nakamura T; Sakaguchi S. 2004. Distinct contribution of IL-6, TNF-alpha, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice. J Clin Invest 114(4):582-8. [PubMed: 15314695]  [MGI Ref ID J:92002]

Heinzel FP; Maier RA Jr. 1999. Interleukin-4-independent acceleration of cutaneous leishmaniasis in susceptible BALB/c mice following treatment with anti-CTLA4 antibody. Infect Immun 67(12):6454-60. [PubMed: 10569763]  [MGI Ref ID J:58540]

Hepworth MR; Grencis RK. 2009. Disruption of Th2 immunity results in a gender-specific expansion of IL-13 producing accessory NK cells during helminth infection. J Immunol 183(6):3906-14. [PubMed: 19692641]  [MGI Ref ID J:152324]

Hernandez-Pando R; Aguilar D; Hernandez ML; Orozco H; Rook G. 2004. Pulmonary tuberculosis in BALB/c mice with non-functional IL-4 genes: changes in the inflammatory effects of TNF-alpha and in the regulation of fibrosis. Eur J Immunol 34(1):174-83. [PubMed: 14971043]  [MGI Ref ID J:87666]

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]

Herrick CA; MacLeod H; Glusac E; Tigelaar RE; Bottomly K. 2000. Th2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4. J Clin Invest 105(6):765-75. [PubMed: 10727445]  [MGI Ref ID J:61145]

Hiraoka S; Takeuchi N; Bian Y; Nakahara H; Kogo M; Dunussi-Joannopoulos K; Wolf S; Ono S; Fujiwara H. 2005. B7.2-Ig fusion proteins enhance IL-4-dependent differentiation of tumor-sensitized CD8+ cytotoxic T lymphocyte precursors. Int Immunol 17(8):1071-9. [PubMed: 16027141]  [MGI Ref ID J:99968]

Hogan SP; Matthaei KI; Young JM; Koskinen A; Young IG; Foster PS. 1998. A novel T cell-regulated mechanism modulating allergen-induced airways hyperreactivity in BALB/c mice independently of IL-4 and IL-5. J Immunol 161(3):1501-9. [PubMed: 9686617]  [MGI Ref ID J:48882]

Inoue Y; Konieczny BT; Wagener ME; McKenzie AN; Lakkis FG. 2001. Failure to induce neonatal tolerance in mice that lack both IL-4 and IL-13 but not in those that lack IL-4 alone. J Immunol 167(2):1125-8. [PubMed: 11441125]  [MGI Ref ID J:106687]

Iseki M; Omori-Miyake M; Xu W; Sun X; Takaki S; Rawlings DJ; Ziegler SF. 2012. Thymic stromal lymphopoietin (TSLP)-induced polyclonal B-cell activation and autoimmunity are mediated by CD4+ T cells and IL-4. Int Immunol 24(3):183-95. [PubMed: 22281511]  [MGI Ref ID J:182756]

Jessup HK; Brewer AW; Omori M; Rickel EA; Budelsky AL; Yoon BR; Ziegler SF; Comeau MR. 2008. Intradermal administration of thymic stromal lymphopoietin induces a T cell- and eosinophil-dependent systemic Th2 inflammatory response. J Immunol 181(6):4311-9. [PubMed: 18768889]  [MGI Ref ID J:139079]

Johnson JR; Swirski FK; Gajewska BU; Wiley RE; Fattouh R; Pacitto SR; Wong JK; Stampfli MR; Jordana M. 2007. Divergent immune responses to house dust mite lead to distinct structural-functional phenotypes. Am J Physiol Lung Cell Mol Physiol 293(3):L730-9. [PubMed: 17586699]  [MGI Ref ID J:128039]

Jones TG; Hallgren J; Humbles A; Burwell T; Finkelman FD; Alcaide P; Austen KF; Gurish MF. 2009. Antigen-induced increases in pulmonary mast cell progenitor numbers depend on IL-9 and CD1d-restricted NKT cells. J Immunol 183(8):5251-60. [PubMed: 19783672]  [MGI Ref ID J:153832]

Khodoun M; Lewis CC; Yang JQ; Orekov T; Potter C; Wynn T; Mentink-Kane M; Hershey GK; Wills-Karp M; Finkelman FD. 2007. Differences in expression, affinity, and function of soluble (s)IL-4Ralpha and sIL-13Ralpha2 suggest opposite effects on allergic responses. J Immunol 179(10):6429-38. [PubMed: 17982031]  [MGI Ref ID J:153871]

Kitajima M; Lee HC; Nakayama T; Ziegler SF. 2011. TSLP enhances the function of helper type 2 cells. Eur J Immunol 41(7):1862-71. [PubMed: 21484783]  [MGI Ref ID J:177311]

Kodera T; McGaha TL; Phelps R; Paul WE; Bona CA. 2002. Disrupting the IL-4 gene rescues mice homozygous for the tight-skin mutation from embryonic death and diminishes TGF-beta production by fibroblasts. Proc Natl Acad Sci U S A 99(6):3800-5. [PubMed: 11891315]  [MGI Ref ID J:75471]

Kolodsick JE; Toews GB; Jakubzick C; Hogaboam C; Moore TA; McKenzie A; Wilke CA; Chrisman CJ; Moore BB. 2004. Protection from fluorescein isothiocyanate-induced fibrosis in IL-13-deficient, but not IL-4-deficient, mice results from impaired collagen synthesis by fibroblasts. J Immunol 172(7):4068-76. [PubMed: 15034018]  [MGI Ref ID J:88681]

Komine O; Hayashi K; Natsume W; Watanabe T; Seki Y; Seki N; Yagi R; Sukzuki W; Tamauchi H; Hozumi K; Habu S; Kubo M; Satake M. 2003. The Runx1 Transcription Factor Inhibits the Differentiation of Naive CD4+ T Cells into the Th2 Lineage by Repressing GATA3 Expression. J Exp Med 198(1):51-61. [PubMed: 12835475]  [MGI Ref ID J:84459]

Kopf M; Brombacher F; Kohler G; Kienzle G; Widmann KH; Lefrang K; Humborg C; Ledermann B; Solbach W. 1996. IL-4-deficient Balb/c mice resist infection with Leishmania major. J Exp Med 184(3):1127-36. [PubMed: 9064329]  [MGI Ref ID J:35236]

Kropf P; Schopf LR; Chung CL; Xu D; Liew FY; Sypek JP; Muller I. 1999. Expression of Th2 cytokines and the stable Th2 marker ST2L in the absence of IL-4 during Leishmania major infection. Eur J Immunol 29(11):3621-8. [PubMed: 10556817]  [MGI Ref ID J:115123]

Mangashetti LS; Khapli SM; Wani MR. 2005. IL-4 inhibits bone-resorbing activity of mature osteoclasts by affecting NF-kappa B and Ca2+ signaling. J Immunol 175(2):917-25. [PubMed: 16002690]  [MGI Ref ID J:100700]

Maroof A; Penny M; Kingston R; Murray C; Islam S; Bedford PA; Knight SC. 2006. Interleukin-4 can induce interleukin-4 production in dendritic cells. Immunology 117(2):271-9. [PubMed: 16423063]  [MGI Ref ID J:106772]

McDermott JR; Leslie FC; D'Amato M; Thompson DG; Grencis RK; McLaughlin JT. 2006. Immune control of food intake: enteroendocrine cells are regulated by CD4+ T lymphocytes during small intestinal inflammation. Gut 55(4):492-7. [PubMed: 16299028]  [MGI Ref ID J:195108]

Metwali A; Elliott D; Blum AM; Li J; Sandor M; Lynch R; Noben-Trauth N; Weinstock JV. 1996. The granulomatous response in murine Schistosomiasis mansoni does not switch to Th1 in IL-4-deficient C57BL/6 mice. J Immunol 157(10):4546-53. [PubMed: 8906833]  [MGI Ref ID J:37196]

Mirmonsef P; Shelburne CP; Fitzhugh Yeatman C 2nd; Chong HJ; Ryan JJ. 1999. Inhibition of Kit expression by IL-4 and IL-10 in murine mast cells: role of STAT6 and phosphatidylinositol 3'-kinase. J Immunol 163(5):2530-9. [PubMed: 10452990]  [MGI Ref ID J:57096]

Mishra PK; Wu W; Rozo C; Hallab NJ; Benevenia J; Gause WC. 2011. Micrometer-sized titanium particles can induce potent Th2-type responses through TLR4-independent pathways. J Immunol 187(12):6491-8. [PubMed: 22095717]  [MGI Ref ID J:180376]

Mohrs M; Ledermann B; Kohler G; Dorfmuller A; Gessner A; Brombacher F. 1999. Differences between IL-4- and IL-4 receptor alpha-deficient mice in chronic leishmaniasis reveal a protective role for IL-13 receptor signaling. J Immunol 162(12):7302-8. [PubMed: 10358179]  [MGI Ref ID J:55526]

Morimoto Y; Bian Y; Gao P; Yashiro-Ohtani Y; Zhou XY; Ono S; Nakahara H; Kogo M; Hamaoka T; Fujiwara H. 2005. Induction of surface CCR4 and its functionality in mouse Th2 cells is regulated differently during Th2 development. J Leukoc Biol 78(3):753-61. [PubMed: 16126843]  [MGI Ref ID J:100501]

Morris SC; Heidorn SM; Herbert DR; Perkins C; Hildeman DA; Khodoun MV; Finkelman FD. 2009. Endogenously produced IL-4 nonredundantly stimulates CD8+ T cell proliferation. J Immunol 182(3):1429-38. [PubMed: 19155490]  [MGI Ref ID J:144327]

Nagayama Y; Saitoh O; McLachlan SM; Rapoport B; Kano H; Kumazawa Y. 2004. TSH receptor-adenovirus-induced Graves' hyperthyroidism is attenuated in both interferon-gamma and interleukin-4 knockout mice; implications for the Th1/Th2 paradigm. Clin Exp Immunol 138(3):417-22. [PubMed: 15544617]  [MGI Ref ID J:94577]

Njoku DB; Li Z; Washington ND; Mellerson JL; Talor MV; Sharma R; Rose NR. 2009. Suppressive and pro-inflammatory roles for IL-4 in the pathogenesis of experimental drug-induced liver injury. Eur J Immunol 39(6):1652-63. [PubMed: 19499520]  [MGI Ref ID J:149435]

Noben-Trauth N. 2000. Susceptibility to Leishmania major infection in the absence of IL-4. Immunol Lett 75(1):41-4. [PubMed: 11163865]  [MGI Ref ID J:66151]

Noben-Trauth N; Hu-Li J; Paul WE. 2000. Conventional, naive CD4+ T cells provide an initial source of IL-4 during Th2 differentiation. J Immunol 165(7):3620-5. [PubMed: 11034364]  [MGI Ref ID J:119587]

Noben-Trauth N; Kropf P; Muller I. 1996. Susceptibility to Leishmania major infection in interleukin-4-deficient mice [see comments] Science 271(5251):987-90. [PubMed: 8584936]  [MGI Ref ID J:31486]

Osawa E; Nakajima A; Fujisawa T; Kawamura YI; Toyama-Sorimachi N; Nakagama H; Dohi T. 2006. Predominant T helper type 2-inflammatory responses promote murine colon cancers. Int J Cancer 118(9):2232-6. [PubMed: 16331625]  [MGI Ref ID J:107259]

Panthel K; Faller G; Haas R. 2003. Colonization of C57BL/6J and BALB/c wild-type and knockout mice with Helicobacter pylori: effect of vaccination and implications for innate and acquired immunity. Infect Immun 71(2):794-800. [PubMed: 12540559]  [MGI Ref ID J:81703]

Perona-Wright G; Mohrs K; Mohrs M. 2010. Sustained signaling by canonical helper T cell cytokines throughout the reactive lymph node. Nat Immunol 11(6):520-6. [PubMed: 20418876]  [MGI Ref ID J:160618]

Petritus PM; Burns JM Jr. 2008. Suppression of lethal Plasmodium yoelii malaria following protective immunization requires antibody-, IL-4-, and IFN-gamma-dependent responses induced by vaccination and/or challenge infection. J Immunol 180(1):444-53. [PubMed: 18097046]  [MGI Ref ID J:130916]

Pillai AB; George TI; Dutt S; Strober S. 2009. Host natural killer T cells induce an interleukin-4-dependent expansion of donor CD4+CD25+Foxp3+ T regulatory cells that protects against graft-versus-host disease. Blood 113(18):4458-67. [PubMed: 19221040]  [MGI Ref ID J:148423]

Potter MR; Noben-Trauth N; Weis JH; Teuscher C; Weis JJ. 2000. Interleukin-4 (IL-4) and IL-13 signaling pathways Do not regulate borrelia burgdorferi-induced arthritis in mice: IgG1 is not required for host control of tissue spirochetes Infect Immun 68(10):5603-9. [PubMed: 10992460]  [MGI Ref ID J:64838]

Saraiva M; Christensen JR; Veldhoen M; Murphy TL; Murphy KM; O'Garra A. 2009. Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose. Immunity 31(2):209-19. [PubMed: 19646904]  [MGI Ref ID J:151873]

Sasaki H; Hou L; Belani A; Wang CY; Uchiyama T; Muller R; Stashenko P. 2000. IL-10, but not IL-4, suppresses infection-stimulated bone resorption in vivo. J Immunol 165(7):3626-30. [PubMed: 11034365]  [MGI Ref ID J:118728]

Schuler T; Qin Z; Ibe S; Noben-Trauth N; Blankenstein T. 1999. T helper cell type 1-associated and cytotoxic T lymphocyte-mediated tumor immunity is impaired in interleukin 4-deficient mice. J Exp Med 189(5):803-10. [PubMed: 10049944]  [MGI Ref ID J:53801]

Schwarze J; Cieslewicz G; Hamelmann E; Joetham A; Shultz LD; Lamers MC; Gelfand EW. 1999. IL-5 and eosinophils are essential for the development of airway hyperresponsiveness following acute respiratory syncytial virus infection. J Immunol 162(5):2997-3004. [PubMed: 10072551]  [MGI Ref ID J:110844]

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Sokol CL; Barton GM; Farr AG; Medzhitov R. 2008. A mechanism for the initiation of allergen-induced T helper type 2 responses. Nat Immunol 9(3):310-8. [PubMed: 18300366]  [MGI Ref ID J:131552]

Sosinowski T; White JT; Cross EW; Haluszczak C; Marrack P; Gapin L; Kedl RM. 2013. CD8alpha+ Dendritic Cell Trans Presentation of IL-15 to Naive CD8+ T Cells Produces Antigen-Inexperienced T Cells in the Periphery with Memory Phenotype and Function. J Immunol 190(5):1936-47. [PubMed: 23355737]  [MGI Ref ID J:193471]

Spencer L; Shultz L; Rajan TV. 2001. Interleukin-4 receptor-stat6 signaling in murine infections with a tissue-dwelling nematode parasite. Infect Immun 69(12):7743-52. [PubMed: 11705956]  [MGI Ref ID J:73137]

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Steenwinckel V; Louahed J; Lemaire MM; Sommereyns C; Warnier G; McKenzie A; Brombacher F; Van Snick J; Renauld JC. 2009. IL-9 promotes IL-13-dependent paneth cell hyperplasia and up-regulation of innate immunity mediators in intestinal mucosa. J Immunol 182(8):4737-43. [PubMed: 19342650]  [MGI Ref ID J:147735]

Tawara I; Maeda Y; Sun Y; Lowler KP; Liu C; Toubai T; McKenzie AN; Reddy P. 2008. Combined Th2 cytokine deficiency in donor T cells aggravates experimental acute graft-vs-host disease. Exp Hematol 36(8):988-96. [PubMed: 18410989]  [MGI Ref ID J:139377]

Urban JF Jr; Noben-Trauth N; Donaldson DD; Madden KB; Morris SC; Collins M; Finkelman FD. 1998. IL-13, IL-4Ralpha, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis. Immunity 8(2):255-64. [PubMed: 9492006]  [MGI Ref ID J:110429]

Van den Bossche J; Bogaert P; van Hengel J; Guerin CJ; Berx G; Movahedi K; Van den Bergh R; Pereira-Fernandes A; Geuns JM; Pircher H; Dorny P; Grooten J; De Baetselier P; Van Ginderachter JA. 2009. Alternatively activated macrophages engage in homotypic and heterotypic interactions through IL-4 and polyamine-induced E-cadherin/catenin complexes. Blood 114(21):4664-74. [PubMed: 19726720]  [MGI Ref ID J:155503]

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Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryThe strain is maintained by homozygous sibling matings. Expected coat color from breeding:Albino
Mating SystemHomozygote x Homozygote         (Female x Male)   01-MAR-06
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $195.00Female or MaleHomozygous for Il4tm2Nnt  
Price per Pair (US dollars $)Pair Genotype
$390.00Homozygous for Il4tm2Nnt x Homozygous for Il4tm2Nnt  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $253.50Female or MaleHomozygous for Il4tm2Nnt  
Price per Pair (US dollars $)Pair Genotype
$507.00Homozygous for Il4tm2Nnt x Homozygous for Il4tm2Nnt  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

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.
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JAX® Mice
Surgical and Preconditioning Services
JAX® Services
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Terms of Use

Terms of Use


General Terms and Conditions


Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

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.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON 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, 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.


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