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) Species laboratory mouse Background Strain C57BL/6 Donor Strain 129S1 via W9.5 ES (+Kitl-SlJ) cell line Generation N11F36 (06-JAN-09)   Donating Investigator Jeanne Magram,   Boehringer Ingelheim Pharmaceuticals,Inc

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Il12a^tm1Jm targeted mutation on a normally resistant 129/Sv genetic background are unable to restrict the progression of Leishmania major infection, demonstrating the importance of this cytokine for developing such resistance. Homozygotes are unable to mount a delayed-type hypersensitivity (DTH) reaction but a TH2 response is induced. Also known as p35. Please refer to the Il12b-deficient related targeted mutations (Stock No. 002693 and 002694).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
The targeting strategy removed exons 1 and 2 from the Il12a gene.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Il12a^tm1Jm allele

002691

C.129S1(B6)-Il12atm1Jm/J

View Strains carrying   Il12a^tm1Jm     (1 strain)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Il12a^tm1Jm/Il12a^tm1Jm

        B6.129S1-Il12a^tm1Jm/J

• tumorigenesis
• increased incidence of chemically-induced tumors (MGI Ref ID J:111568)
  • earlier tumor appearance and increased incidence of papillomas compared to wild-type mice after treatment with DMBA and TPA in a 2 step skin carcinogenesis protocol
  • however, resistance to tumor formation following intradermal challenge with with PDV squamous carcinoma cells is similar to wild-type mice
• homeostasis/metabolism phenotype
• increased incidence of chemically-induced tumors (MGI Ref ID J:111568)
  • earlier tumor appearance and increased incidence of papillomas compared to wild-type mice after treatment with DMBA and TPA in a 2 step skin carcinogenesis protocol
  • however, resistance to tumor formation following intradermal challenge with with PDV squamous carcinoma cells is similar to wild-type mice

Il12a^tm1Jm/Il12a^tm1Jm

        B6.129S1-Il12a^tm1Jm

• immune system phenotype
• *normal* immune system phenotype (MGI Ref ID J:120806)
  • no abnormal response to infection is detected

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

Il12a^tm1Jm/Il12a^tm1Jm

        129S1/Sv-Il12a^tm1Jm

• immune system phenotype
• abnormal CD4-positive T cell physiology (MGI Ref ID J:34164)
  • 75 days after infection Il4 mRNA expression in CD4+ cells is 100-fold higher than in wild-type
  • 75 days after infection Ifng mRNA expression in CD4+ cells is more than 50-fold lower than in wild-type
  • draining lymph node cells in L. major infected mice produce significantly more IL4 compared to IFNG in contrast to wild-type mice which express more IFNG than IL4
• decreased susceptibility to type IV hypersensitivity reaction (MGI Ref ID J:34164)
  • do not show any delayed type hypersensitivity response to application of Leishmania antigen to the uninfected footpad 41 days after initial infection with L. major
• increased susceptibility to parasitic infection (MGI Ref ID J:34164)
  • develop large lesions unlike wild-type 129S1/Sv mice after infection with Leishmania major
  • 75 days after infection with L. major parasite numbers in the draining lymph nodes are increased 80-fold compared to wild-type mice

Il12a^tm1Jm/Il12a^tm1Jm

        C.129S1-Il12a^tm1Jm

• immune system phenotype
• impaired NK cell cytolysis (MGI Ref ID J:125611)
  • following infection with Leishmania infantum

Il12a^tm1Jm/Il12a^tm1Jm

        involves: 129S1/Sv

• immune system phenotype
• abnormal NK cell physiology (MGI Ref ID J:139001)
  • NK cells in vivo make much about 7-fold less IFN-gamma in response to injections of the TLR9 agonist CpG

View Research Applications

Research Applications

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

Il12a^tm1Jm related

Cancer Research
Growth Factors/Receptors/Cytokines

Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines

Genes & Alleles

Gene & Allele Information

Allele Symbol		Il12atm1Jm
Allele Name		targeted mutation 1, Jeanne Magram
Allele Type		Targeted (knock-out)
Common Name(s)		IL-12p35; Il12a-; Il12p35-; p35-;
Mutation Made By		Jeanne Magram,   Boehringer Ingelheim Pharmaceuticals,Inc
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line Name		W9.5/W95
ES Cell Line Strain		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name		Il12a, interleukin 12a
Chromosome		3
Gene Common Name(s)		CLMF; IL-12A; IL-12p35; Il-12a; NFSK; NKSF1; P35;
Molecular Note		A neomycin resistance cassette replaced exons 1 and 2 of the gene. [MGI Ref ID J:34164]

Genotyping

Genotyping Information

Genotyping Protocols

Il12a^tm1Jm, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Mattner F; Magram J; Ferrante J; Launois P; Di Padova K; Behin R; Gately MK; Louis JA; Alber G. 1996. Genetically resistant mice lacking interleukin-12 are susceptible to infection with Leishmania major and mount a polarized Th2 cell response. Eur J Immunol 26(7):1553-9. [PubMed: 8766560]  [MGI Ref ID J:34164]

Additional References

Bitsaktsis C; Huntington J; Winslow G. 2004. Production of IFN-gamma by CD4 T cells is essential for resolving ehrlichia infection. J Immunol 172(11):6894-901. [PubMed: 15153508]  [MGI Ref ID J:90518]

Cua DJ; Sherlock J; Chen Y; Murphy CA; Joyce B; Seymour B; Lucian L; To W; Kwan S; Churakova T; Zurawski S; Wiekowski M; Lira SA; Gorman D; Kastelein RA; Sedgwick JD. 2003. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421(6924):744-8. [PubMed: 12610626]  [MGI Ref ID J:89968]

Hazlett LD; Rudner XL; McClellan SA; Barrett RP; Lighvani S. 2002. Role of IL-12 and IFN-gamma in Pseudomonas aeruginosa corneal infection. Invest Ophthalmol Vis Sci 43(2):419-24. [PubMed: 11818386]  [MGI Ref ID J:74264]

Il12a^tm1Jm related

Becher B; Durell BG; Noelle RJ. 2002. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J Clin Invest 110(4):493-7. [PubMed: 12189243]  [MGI Ref ID J:78574]

Birkner K; Steiner B; Rinkler C; Kern Y; Aichele P; Bogdan C; von Loewenich FD. 2008. The elimination of Anaplasma phagocytophilum requires CD4(+) T cells, but is independent of Th1 cytokines and a wide spectrum of effector mechanisms. Eur J Immunol 38(12):3395-3410. [PubMed: 19039769]  [MGI Ref ID J:141369]

Bitsaktsis C; Huntington J; Winslow G. 2004. Production of IFN-gamma by CD4 T cells is essential for resolving ehrlichia infection. J Immunol 172(11):6894-901. [PubMed: 15153508]  [MGI Ref ID J:90518]

Bitsaktsis C; Nandi B; Racine R; MacNamara KC; Winslow G. 2007. T-Cell-independent humoral immunity is sufficient for protection against fatal intracellular ehrlichia infection. Infect Immun 75(10):4933-41. [PubMed: 17664264]  [MGI Ref ID J:125283]

Brombacher F; Dorfmuller A; Magram J; Dai WJ; Kohler G; Wunderlin A; Palmer-Lehmann K; Gately MK; Alber G. 1999. IL-12 is dispensable for innate and adaptive immunity against low doses of Listeria monocytogenes. Int Immunol 11(3):325-32. [PubMed: 10221644]  [MGI Ref ID J:110544]

Camoglio L; Juffermans NP; Peppelenbosch M; te Velde AA; ten Kate FJ; van Deventer SJ; Kopf M. 2002. Contrasting roles of IL-12p40 and IL-12p35 in the development of hapten-induced colitis. Eur J Immunol 32(1):261-9. [PubMed: 11782017]  [MGI Ref ID J:73931]

Chackerian AA; Chen SJ; Brodie SJ; Mattson JD; McClanahan TK; Kastelein RA; Bowman EP. 2006. Neutralization or absence of the interleukin-23 pathway does not compromise immunity to mycobacterial infection. Infect Immun 74(11):6092-9. [PubMed: 16923792]  [MGI Ref ID J:113448]

Chang JT; Shevach EM; Segal BM. 1999. Regulation of interleukin (IL)-12 receptor beta2 subunit expression by endogenous IL-12: a critical step in the differentiation of pathogenic autoreactive T cells. J Exp Med 189(6):969-78. [PubMed: 10075980]  [MGI Ref ID J:53619]

Chang SR; Wang KJ; Lu YF; Yang LJ; Chen WJ; Lin YH; Chang HH; Wang SL. 2007. Characterization of Early Gamma Interferon (IFN-{gamma}) Expression during Murine Listeriosis: Identification of NK1.1+ CD11c+ Cells as the Primary IFN-{gamma}-Expressing Cells. Infect Immun 75(3):1167-76. [PubMed: 17158904]  [MGI Ref ID J:118505]

Chen Z; Duan RS; Q HC; Wu Q; Mix E; Winblad B; Ljunggren HG; Zhu J. 2004. IL-12p35 deficiency alleviates kainic acid-induced hippocampal neurodegeneration in C57BL/6 mice. Neurobiol Dis 17(2):171-8. [PubMed: 15474355]  [MGI Ref ID J:120018]

Collison LW; Workman CJ; Kuo TT; Boyd K; Wang Y; Vignali KM; Cross R; Sehy D; Blumberg RS; Vignali DA. 2007. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450(7169):566-9. [PubMed: 18033300]  [MGI Ref ID J:127800]

Cooper AM; Kipnis A; Turner J; Magram J; Ferrante J; Orme IM. 2002. Mice lacking bioactive IL-12 can generate protective, antigen-specific cellular responses to mycobacterial infection only if the IL-12 p40 subunit is present. J Immunol 168(3):1322-7. [PubMed: 11801672]  [MGI Ref ID J:73949]

Cua DJ; Sherlock J; Chen Y; Murphy CA; Joyce B; Seymour B; Lucian L; To W; Kwan S; Churakova T; Zurawski S; Wiekowski M; Lira SA; Gorman D; Kastelein RA; Sedgwick JD. 2003. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421(6924):744-8. [PubMed: 12610626]  [MGI Ref ID J:89968]

Denkinger CM; Denkinger MD; Forsthuber TG. 2007. Pertussis toxin-induced cytokine differentiation and clonal expansion of T cells is mediated predominantly via costimulation. Cell Immunol 246(1):46-54. [PubMed: 17601518]  [MGI Ref ID J:123551]

Dokun AO; Chu DT; Yang L; Bendelac AS; Yokoyama WM. 2001. Analysis of in situ NK cell responses during viral infection. J Immunol 167(9):5286-93. [PubMed: 11673544]  [MGI Ref ID J:72673]

Doodes PD; Cao Y; Hamel KM; Wang Y; Farkas B; Iwakura Y; Finnegan A. 2008. Development of proteoglycan-induced arthritis is independent of IL-17. J Immunol 181(1):329-37. [PubMed: 18566398]  [MGI Ref ID J:137406]

Doolan DL; Hoffman SL. 1999. IL-12 and NK cells are required for antigen-specific adaptive immunity against malaria initiated by CD8+ T cells in the Plasmodium yoelii model. J Immunol 163(2):884-92. [PubMed: 10395683]  [MGI Ref ID J:119784]

Esche C; Gambotto A; Satoh Y; Gerein V; Robbins PD; Watkins SC; Lotze MT; Shurin MR. 1999. CD154 inhibits tumor-induced apoptosis in dendritic cells and tumor growth. Eur J Immunol 29(7):2148-55. [PubMed: 10427977]  [MGI Ref ID J:115301]

Esche C; Subbotin VM; Hunter O; Peron JM; Maliszewski C; Lotze MT; Shurin MR. 1999. Differential regulation of epidermal and dermal dendritic cells by IL-12 and Flt3 ligand. J Invest Dermatol 113(6):1028-32. [PubMed: 10594747]  [MGI Ref ID J:118447]

Evel-Kabler K; Song XT; Aldrich M; Huang XF; Chen SY. 2006. SOCS1 restricts dendritic cells' ability to break self tolerance and induce antitumor immunity by regulating IL-12 production and signaling. J Clin Invest 116(1):90-100. [PubMed: 16357940]  [MGI Ref ID J:105256]

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]

Feng CG; Kaviratne M; Rothfuchs AG; Cheever A; Hieny S; Young HA; Wynn TA; Sher A. 2006. NK cell-derived IFN-gamma differentially regulates innate resistance and neutrophil response in T cell-deficient hosts infected with Mycobacterium tuberculosis. J Immunol 177(10):7086-93. [PubMed: 17082625]  [MGI Ref ID J:140483]

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]

Gorbachev AV; Fairchild RL. 2004. CD40 engagement enhances antigen-presenting langerhans cell priming of IFN-gamma-producing CD4+ and CD8+ T cells independently of IL-12. J Immunol 173(4):2443-52. [PubMed: 15294958]  [MGI Ref ID J:92689]

Gran B; Zhang GX; Yu S; Li J; Chen XH; Ventura ES; Kamoun M; Rostami A. 2002. IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination. J Immunol 169(12):7104-10. [PubMed: 12471147]  [MGI Ref ID J:118415]

Gutcher I; Urich E; Wolter K; Prinz M; Becher B. 2006. Interleukin 18-independent engagement of interleukin 18 receptor-alpha is required for autoimmune inflammation. Nat Immunol 7(9):946-53. [PubMed: 16906165]  [MGI Ref ID J:112650]

Happel KI; Dubin PJ; Zheng M; Ghilardi N; Lockhart C; Quinton LJ; Odden AR; Shellito JE; Bagby GJ; Nelson S; Kolls JK. 2005. Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. J Exp Med 202(6):761-9. [PubMed: 16157683]  [MGI Ref ID J:107457]

Hazlett LD; Rudner XL; McClellan SA; Barrett RP; Lighvani S. 2002. Role of IL-12 and IFN-gamma in Pseudomonas aeruginosa corneal infection. Invest Ophthalmol Vis Sci 43(2):419-24. [PubMed: 11818386]  [MGI Ref ID J:74264]

Henry CJ; Ornelles DA; Mitchell LM; Brzoza-Lewis KL; Hiltbold EM. 2008. IL-12 produced by dendritic cells augments CD8+ T cell activation through the production of the chemokines CCL1 and CCL17. J Immunol 181(12):8576-84. [PubMed: 19050277]  [MGI Ref ID J:142058]

Holscher C; Atkinson RA; Arendse B; Brown N; Myburgh E; Alber G; Brombacher F. 2001. A protective and agonistic function of IL-12p40 in mycobacterial infection. J Immunol 167(12):6957-66. [PubMed: 11739515]  [MGI Ref ID J:73093]

Hong KJ; Wickstrum JR; Yeh HW; Parmely MJ. 2007. Toll-like receptor 2 controls the gamma interferon response to Francisella tularensis by mouse liver lymphocytes. Infect Immun 75(11):5338-45. [PubMed: 17785474]  [MGI Ref ID J:126365]

Hou B; Reizis B; Defranco AL. 2008. Toll-like Receptors Activate Innate and Adaptive Immunity by using Dendritic Cell-Intrinsic and -Extrinsic Mechanisms. Immunity 29(2):272-82. [PubMed: 18656388]  [MGI Ref ID J:139001]

Huaux F; Arras M; Tomasi D; Barbarin V; Delos M; Coutelier JP; Vink A; Phan SH; Renauld JC; Lison D. 2002. A profibrotic function of IL-12p40 in experimental pulmonary fibrosis. J Immunol 169(5):2653-61. [PubMed: 12193738]  [MGI Ref ID J:120205]

Khader SA; Bell GK; Pearl JE; Fountain JJ; Rangel-Moreno J; Cilley GE; Shen F; Eaton SM; Gaffen SL; Swain SL; Locksley RM; Haynes L; Randall TD; Cooper AM. 2007. IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat Immunol 8(4):369-77. [PubMed: 17351619]  [MGI Ref ID J:120806]

Khader SA; Partida-Sanchez S; Bell G; Jelley-Gibbs DM; Swain S; Pearl JE; Ghilardi N; Desauvage FJ; Lund FE; Cooper AM. 2006. Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection. J Exp Med 203(7):1805-15. [PubMed: 16818672]  [MGI Ref ID J:124401]

Khader SA; Pearl JE; Sakamoto K; Gilmartin L; Bell GK; Jelley-Gibbs DM; Ghilardi N; deSauvage F; Cooper AM. 2005. IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available. J Immunol 175(2):788-95. [PubMed: 16002675]  [MGI Ref ID J:100721]

Kim SJ; Caton M; Wang C; Khalil M; Zhou ZJ; Hardin J; Diamond B. 2008. Increased IL-12 inhibits B cells' differentiation to germinal center cells and promotes differentiation to short-lived plasmablasts. J Exp Med 205(10):2437-48. [PubMed: 18809711]  [MGI Ref ID J:140103]

Kleinman ME; Yamada K; Takeda A; Chandrasekaran V; Nozaki M; Baffi JZ; Albuquerque RJ; Yamasaki S; Itaya M; Pan Y; Appukuttan B; Gibbs D; Yang Z; Kariko K; Ambati BK; Wilgus TA; DiPietro LA; Sakurai E; Zhang K; Smith JR; Taylor EW; Ambati J. 2008. Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature 452(7187):591-7. [PubMed: 18368052]  [MGI Ref ID J:133772]

Kleinschek MA; Muller U; Brodie SJ; Stenzel W; Kohler G; Blumenschein WM; Straubinger RK; McClanahan T; Kastelein RA; Alber G. 2006. IL-23 enhances the inflammatory cell response in Cryptococcus neoformans infection and induces a cytokine pattern distinct from IL-12. J Immunol 176(2):1098-106. [PubMed: 16393998]  [MGI Ref ID J:126443]

Langowski JL; Zhang X; Wu L; Mattson JD; Chen T; Smith K; Basham B; McClanahan T; Kastelein RA; Oft M. 2006. IL-23 promotes tumour incidence and growth. Nature 442(7101):461-5. [PubMed: 16688182]  [MGI Ref ID J:111568]

Lee HH; Hoeman CM; Hardaway JC; Guloglu FB; Ellis JS; Jain R; Divekar R; Tartar DM; Haymaker CL; Zaghouani H. 2008. Delayed maturation of an IL-12-producing dendritic cell subset explains the early Th2 bias in neonatal immunity. J Exp Med 205(10):2269-80. [PubMed: 18762566]  [MGI Ref ID J:141185]

Lieberman LA; Cardillo F; Owyang AM; Rennick DM; Cua DJ; Kastelein RA; Hunter CA. 2004. IL-23 provides a limited mechanism of resistance to acute toxoplasmosis in the absence of IL-12. J Immunol 173(3):1887-93. [PubMed: 15265921]  [MGI Ref ID J:92028]

Liese J; Schleicher U; Bogdan C. 2007. TLR9 signaling is essential for the innate NK cell response in murine cutaneous leishmaniasis. Eur J Immunol 37(12):3424-34. [PubMed: 18034422]  [MGI Ref ID J:141551]

Liu CH; Fan YT; Dias A; Esper L; Corn RA; Bafica A; Machado FS; Aliberti J. 2006. Cutting edge: dendritic cells are essential for in vivo IL-12 production and development of resistance against Toxoplasma gondii infection in mice. J Immunol 177(1):31-5. [PubMed: 16785494]  [MGI Ref ID J:134413]

Liu J; Xiang Z; Ma X. 2004. Role of IFN regulatory factor-1 and IL-12 in immunological resistance to pathogenesis of N-methyl-N-nitrosourea-induced T lymphoma. J Immunol 173(2):1184-93. [PubMed: 15240709]  [MGI Ref ID J:91927]

Liu R; Van Kaer L; La Cava A; Price M; Campagnolo DI; Collins M; Young DA; Vollmer TL; Shi FD. 2006. Autoreactive T cells mediate NK cell degeneration in autoimmune disease. J Immunol 176(9):5247-54. [PubMed: 16621990]  [MGI Ref ID J:131629]

Lucas M; Schachterle W; Oberle K; Aichele P; Diefenbach A. 2007. Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity 26(4):503-17. [PubMed: 17398124]  [MGI Ref ID J:123584]

Luger D; Silver PB; Tang J; Cua D; Chen Z; Iwakura Y; Bowman EP; Sgambellone NM; Chan CC; Caspi RR. 2008. Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. J Exp Med 205(4):799-810. [PubMed: 18391061]  [MGI Ref ID J:133969]

Maxwell JR; Yadav R; Rossi RJ; Ruby CE; Weinberg AD; Aguila HL; Vella AT. 2006. IL-18 bridges innate and adaptive immunity through IFN-gamma and the CD134 pathway. J Immunol 177(1):234-45. [PubMed: 16785519]  [MGI Ref ID J:134442]

Meeran SM; Katiyar S; Elmets CA; Katiyar SK. 2007. Interleukin-12 deficiency is permissive for angiogenesis in UV radiation-induced skin tumors. Cancer Res 67(8):3785-93. [PubMed: 17440092]  [MGI Ref ID J:120948]

Meeran SM; Mantena SK; Elmets CA; Katiyar SK. 2006. (-)-Epigallocatechin-3-gallate prevents photocarcinogenesis in mice through interleukin-12-dependent DNA repair. Cancer Res 66(10):5512-20. [PubMed: 16707481]  [MGI Ref ID J:109027]

Moreira AP; Campanelli AP; Cavassani KA; Souto JT; Ferreira BR; Martinez R; Rossi MA; Silva JS. 2006. Intercellular adhesion molecule-1 is required for the early formation of granulomas and participates in the resistance of mice to the infection with the fungus Paracoccidioides brasiliensis. Am J Pathol 169(4):1270-81. [PubMed: 17003484]  [MGI Ref ID J:113377]

Mullarky IK; Szaba FM; Berggren KN; Kummer LW; Wilhelm LB; Parent MA; Johnson LL; Smiley ST. 2006. Tumor necrosis factor alpha and gamma interferon, but not hemorrhage or pathogen burden, dictate levels of protective fibrin deposition during infection. Infect Immun 74(2):1181-8. [PubMed: 16428767]  [MGI Ref ID J:104988]

Muller U; Kohler G; Mossmann H; Schaub GA; Alber G; Di Santo JP; Brombacher F; Holscher C. 2001. IL-12-independent IFN-gamma production by T cells in experimental Chagas' disease is mediated by IL-18. J Immunol 167(6):3346-53. [PubMed: 11544324]  [MGI Ref ID J:118724]

Murray HW; Tsai CW; Liu J; Ma X. 2006. Responses to Leishmania donovani in mice deficient in interleukin-12 (IL-12), IL-12/IL-23, or IL-18. Infect Immun 74(7):4370-4. [PubMed: 16790814]  [MGI Ref ID J:110039]

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]

Piccotti JR; Li K; Chan SY; Ferrante J; Magram J; Eichwald EJ; Bishop DK. 1998. Alloantigen-reactive Th1 development in IL-12-deficient mice. J Immunol 160(3):1132-8. [PubMed: 9570526]  [MGI Ref ID J:90552]

Ramirez-Pineda JR; Frohlich A; Berberich C; Moll H. 2004. Dendritic cells (DC) activated by CpG DNA ex vivo are potent inducers of host resistance to an intracellular pathogen that is independent of IL-12 derived from the immunizing DC. J Immunol 172(10):6281-9. [PubMed: 15128817]  [MGI Ref ID J:89850]

Rangachari M; Mauermann N; Marty RR; Dirnhofer S; Kurrer MO; Komnenovic V; Penninger JM; Eriksson U. 2006. T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17. J Exp Med 203(8):2009-19. [PubMed: 16880257]  [MGI Ref ID J:124393]

Reinhardt RL; Hong S; Kang SJ; Wang ZE; Locksley RM. 2006. Visualization of IL-12/23p40 in vivo reveals immunostimulatory dendritic cell migrants that promote Th1 differentiation. J Immunol 177(3):1618-27. [PubMed: 16849470]  [MGI Ref ID J:112745]

Rempel JD; Lewkowich IP; HayGlass KT. 2000. Endogenous IL-12 synthesis is not required to prevent hyperexpression of type 2 cytokine and antibody responses. Eur J Immunol 30(2):347-55. [PubMed: 10671189]  [MGI Ref ID J:115321]

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]

Ruan S; McKinley L; Zheng M; Rudner X; D'Souza A; Kolls JK; Shellito JE. 2008. Interleukin-12 and host defense against murine Pneumocystis pneumonia. Infect Immun 76(5):2130-7. [PubMed: 18332204]  [MGI Ref ID J:134470]

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]

Rutitzky LI; Lopes da Rosa JR; Stadecker MJ. 2005. Severe CD4 T cell-mediated immunopathology in murine schistosomiasis is dependent on IL-12p40 and correlates with high levels of IL-17. J Immunol 175(6):3920-6. [PubMed: 16148138]  [MGI Ref ID J:116693]

Salvatore CM; Fonseca-Aten M; Katz-Gaynor K; Gomez AM; Mejias A; Somers C; Chavez-Bueno S; McCracken GH; Hardy RD. 2007. Respiratory tract infection with Mycoplasma pneumoniae in interleukin-12 knockout mice results in improved bacterial clearance and reduced pulmonary inflammation. Infect Immun 75(1):236-42. [PubMed: 17074851]  [MGI Ref ID J:116650]

Santiago Hda C; Oliveira CF; Santiago L; Ferraz FO; de Souza Dda G; de-Freitas LA; Afonso LC; Teixeira MM; Gazzinelli RT; Vieira LQ. 2004. Involvement of the chemokine RANTES (CCL5) in resistance to experimental infection with Leishmania major. Infect Immun 72(8):4918-23. [PubMed: 15271961]  [MGI Ref ID J:91807]

Satoskar AR; Rodig S; Telford SR 3rd; Satoskar AA; Ghosh SK; von Lichtenberg F; David JR. 2000. IL-12 gene-deficient C57BL/6 mice are susceptible to Leishmania donovani but have diminished hepatic immunopathology. Eur J Immunol 30(3):834-9. [PubMed: 10741399]  [MGI Ref ID J:60891]

Schijns VE; Haagmans BL; Wierda CM; Kruithof B; Heijnen IA; Alber G; Horzinek MC. 1998. Mice lacking IL-12 develop polarized Th1 cells during viral infection. J Immunol 160(8):3958-64. [PubMed: 9558103]  [MGI Ref ID J:46942]

Schleicher U; Liese J; Knippertz I; Kurzmann C; Hesse A; Heit A; Fischer JA; Weiss S; Kalinke U; Kunz S; Bogdan C. 2007. NK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs. J Exp Med 204(4):893-906. [PubMed: 17389237]  [MGI Ref ID J:125611]

Shi M; Ye Z; Umeshappa KS; Moyana T; Xiang J. 2007. Alpha tumor necrosis factor contributes to CD8(+) T cell survival in the transition phase. Biochem Biophys Res Commun 360(3):702-7. [PubMed: 17618911]  [MGI Ref ID J:123025]

Skokos D; Nussenzweig MC. 2007. CD8- DCs induce IL-12-independent Th1 differentiation through Delta 4 Notch-like ligand in response to bacterial LPS. J Exp Med 204(7):1525-31. [PubMed: 17576775]  [MGI Ref ID J:125873]

Sonderegger I; Rohn TA; Kurrer MO; Iezzi G; Zou Y; Kastelein RA; Bachmann MF; Kopf M. 2006. Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune myocarditis. Eur J Immunol 36(11):2849-56. [PubMed: 17039570]  [MGI Ref ID J:116998]

Stokes KY; Clanton EC; Gehrig JL; Granger DN. 2003. Role of interleukin 12 in hypercholesterolemia-induced inflammation. Am J Physiol Heart Circ Physiol 285(6):H2623-9. [PubMed: 12907426]  [MGI Ref ID J:108153]

Sugimoto K; Ogawa A; Shimomura Y; Nagahama K; Mizoguchi A; Bhan AK. 2007. Inducible IL-12-producing B cells regulate Th2-mediated intestinal inflammation. Gastroenterology 133(1):124-36. [PubMed: 17631137]  [MGI Ref ID J:128298]

Takemoto N; Intlekofer AM; Northrup JT; Wherry EJ; Reiner SL. 2006. Cutting Edge: IL-12 inversely regulates T-bet and eomesodermin expression during pathogen-induced CD8+ T cell differentiation. J Immunol 177(11):7515-9. [PubMed: 17114419]  [MGI Ref ID J:140606]

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TeKippe M; Harrison DE; Chen J. 2003. Expansion of hematopoietic stem cell phenotype and activity in Trp53-null mice. Exp Hematol 31(6):521-7. [PubMed: 12829028]  [MGI Ref ID J:115677]

Vossenkamper A; Struck D; Alvarado-Esquivel C; Went T; Takeda K; Akira S; Pfeffer K; Alber G; Lochner M; Forster I; Liesenfeld O. 2004. Both IL-12 and IL-18 contribute to small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii, but IL-12 is dominant over IL-18 in parasite control. Eur J Immunol 34(11):3197-207. [PubMed: 15368276]  [MGI Ref ID J:93844]

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Wieland CW; Florquin S; Pater JM; Weijer S; van der Poll T. 2006. CD4+ cells play a limited role in murine lung infection with Mycobacterium kansasii. Am J Respir Cell Mol Biol 34(2):167-73. [PubMed: 16195537]  [MGI Ref ID J:120194]

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]

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Wu HJ; Sawaya H; Binstadt B; Brickelmaier M; Blasius A; Gorelik L; Mahmood U; Weissleder R; Carulli J; Benoist C; Mathis D. 2007. Inflammatory arthritis can be reined in by CpG-induced DC-NK cell cross talk. J Exp Med 204(8):1911-22. [PubMed: 17646407]  [MGI Ref ID J:125952]

Yen D; Cheung J; Scheerens H; Poulet F; McClanahan T; McKenzie B; Kleinschek MA; Owyang A; Mattson J; Blumenschein W; Murphy E; Sathe M; Cua DJ; Kastelein RA; Rennick D. 2006. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest 116(5):1310-6. [PubMed: 16670770]  [MGI Ref ID J:108946]

Zelante T; De Luca A; Bonifazi P; Montagnoli C; Bozza S; Moretti S; Belladonna ML; Vacca C; Conte C; Mosci P; Bistoni F; Puccetti P; Kastelein RA; Kopf M; Romani L. 2007. IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur J Immunol 37(10):2695-706. [PubMed: 17899546]  [MGI Ref ID J:125340]

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van Den Broek M; Bachmann MF; Kohler G; Barner M; Escher R; Zinkernagel R; Kopf M. 2000. IL-4 and IL-10 antagonize IL-12-mediated protection against acute vaccinia virus infection with a limited role of IFN-gamma and nitric oxide synthetase 2. J Immunol 164(1):371-8. [PubMed: 10605032]  [MGI Ref ID J:125984]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	This strain is maintained by homozygous sibling matings. Expected coat color from breeding:Black
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-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

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
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.

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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.”

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.