Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Background Strain NOD/ShiLt Donor Strain 129S2 Generation [N10F13p]+F13 (05-JAN-08)   Donating Investigator Edward Leiter,   The Jackson Laboratory

Appearance
albino, pink-eyed
Related Genotype: A/? Tyr^c/Tyr^c

Description
Casp1^tm1Sesh homozygous mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. There is no detectable expression of Casp1 in spleen by northern blot analysis or by RT-PCR of peritoneal exudate cells, brain, lung, heart, liver, adrenal gland, kidney, testis, and thymus (Li et al, 1995). Cultured LPS stimulated bone marrow derived macrophages from homozygous NOD.129S2(B6)- Casp1^tm1Sesh /LtJ animals secrete 4-fold less IL1 beta, 30% less IL1 alpha, and IL18 is undetectable when compared with hemizygous and wild-type controls. Diabetes frequency of Casp1^tm1Sesh deficient animals is equivalent to NOD/Lt, heterozygote and wild-type controls. Weanling Casp1^tm1Sesh homozygous animals injected with Complete Freund's adjuvant and young pre-diabetic males treated with multiple low dose streptozotocin behave similarly to control (wild type, heterozygote, or NOD/Lt) animals (Schott et al, 2004). NOD.129S2(B6)- Casp1^tm1Sesh/LtJ is a useful model for studying the role of IL1 and IL18 cytokines in inflammatory processes relating to diabetes.

Development
A construct containing a neomycin expression cassette inserted into exon 6 of Casp1 (cloned from a 129/Sv mouse), deleting 31 bp of sequence encoding the region of the catalytic active site and rendering the sequence out of frame after the insertion, was transfected into D3 (129S2/SvPas derived) embryonic stem cells (ES cells). These ES cells were injected into C57BL/6 blastocysts. Chimeric founders were initially mated to C57BL/6 and subsequently intercrossed to generate homozygotes (Li et al, 1995). In 1998, Dr. Edward Leiter at The Jackson Laboratory received B6.129S2-Casp1^tm1Sesh mice from Dr. Winnie Wong, BASF Bioresearch Corporation and backcrossed this mutation to NOD/Lt for 10 generations, subsequently intercrossing to generate homozygotes (Schott et al. 2004). In 2004, NOD.129S2(B6)- Casp1^tm1Sesh /LtJ homozygous strain at N10F11 was transferred from Edward Leiter's research colony to a Jackson Laboratory distribution colony.

Control Information

	Control
	001976 NOD/ShiLtJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Casp1^tm1Sesh allele

005346

NOD.Cg-Il10tm1Cgn Casp1tm1Sesh/LtJ

View Strains carrying   Casp1^tm1Sesh     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Diabetes Mellitus, Insulin-Dependent; IDDM - Models with phenotypic similarity to human disease where etiologies are distinct.2

2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Casp1^tm1Sesh/Casp1^tm1Sesh

        NOD.129S2(B6)-Casp1^tm1Sesh/LtJ

• immune system phenotype
• decreased interleukin-1 alpha secretion (MGI Ref ID J:87250)
  • cultured LPS-stimulated bone marrow derived macrophages from homozygous mutants secrete 20%-30% less IL-1alpha relative to heterozygous or wild-type (NOD/Lt) mice
• decreased interleukin-1 beta secretion (MGI Ref ID J:87250)
  • cultured LPS-stimulated bone marrow derived macrophages from homozygous mutants secrete 4-fold less IL-1beta relative to heterozygous or wild-type (NOD/Lt) mice
• decreased interleukin-18 secretion (MGI Ref ID J:87250)
  • cultured LPS-stimulated bone marrow derived macrophages from homozygotes produce no immunoreactive IL18 relative to heterozygous or wild-type (NOD/Lt) mice
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype (MGI Ref ID J:87250)
  • homozygotes show no significant differences in the rate or in total incidence of diabetes relative to heterozygotes or wild-type (NOD/Lt) control mice
  • weanling homozygotes injected with Complete Freund's adjuvant and young pre-diabetic males treated with multiple low dose streptozotocin behave similarly to control (wild-type, heterozygous, or NOD/Lt) mice

View Research Applications

Research Applications

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

Casp1^tm1Sesh related

Diabetes and Obesity Research
Type 1 Diabetes (IDDM)

Immunology and Inflammation Research
Immunodeficiency (B cell defects)

Research Tools
Diabetes and Obesity Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Casp1tm1Sesh
Allele Name		targeted mutation 1, Tara Seshadri
Allele Type		Targeted (knock-out)
Common Name(s)		Casp1 -; Caspase-1-; ICE -; casp-1-;
Mutation Made By		Edward Leiter,   The Jackson Laboratory
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Casp1, caspase 1
Chromosome		9
Gene Common Name(s)		Caspase-1; ICE; IL1BC; Il1bc; P45; interleukin 1 beta convertase; interleukin 1 beta-converting enzyme;
Molecular Note		A neomycin expression cassette was inserted into exon 6, deleting 31 bp of sequence encoding the region of the active site and rendering the sequence out of frame after the insertion. Northern blot analysis on spleen RNA demonstrated an absence of the normal transcript in homozygous mice, and western blot analysis showed that the protein was not expressed in peritoneal macrophages of homozygous mice. [MGI Ref ID J:22964]

Genotyping

Genotyping Information

Genotyping Protocols

Casp1^tm1Sesh, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Schott WH; Haskell BD; Tse HM; Milton MJ; Piganelli JD; Choisy-Rossi CM; Reifsnyder PC; Chervonsky AV; Leiter EH. 2004. Caspase-1 Is Not Required for Type 1 Diabetes in the NOD Mouse. Diabetes 53(1):99-104. [PubMed: 14693703]  [MGI Ref ID J:87250]

Additional References

Cumberbatch M; Dearman RJ; Antonopoulos C; Groves RW; Kimber I. 2001. Interleukin (IL)-18 induces Langerhans cell migration by a tumour necrosis factor-alpha- and IL-1beta-dependent mechanism. Immunology 102(3):323-30. [PubMed: 11298831]  [MGI Ref ID J:68644]

Jolicoeur P; Hu C; Mak TW; Martinou JC; Kay DG. 2003. Protection against murine leukemia virus-induced spongiform myeloencephalopathy in mice overexpressing Bcl-2 but not in mice deficient for interleukin-6, inducible nitric oxide synthetase, ICE, Fas, Fas ligand, or TNF-R1 genes. J Virol 77(24):13161-70. [PubMed: 14645573]  [MGI Ref ID J:86761]

Li P; Allen H; Banerjee S; Franklin S; Herzog L; Johnston C; McDowell J; Paskind M; Rodman L; Salfeld J; Towne E; Tracey D; Wardwell S; Wei FY; Wong W; Kamen R; Seshadri T. 1995. Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock. Cell 80(3):401-11. [PubMed: 7859282]  [MGI Ref ID J:22964]

Li P; Allen H; Banerjee S; Seshadri T. 1997. Characterization of mice deficient in interleukin-1 beta converting enzyme. J Cell Biochem 64(1):27-32. [PubMed: 9015751]  [MGI Ref ID J:40691]

Casp1^tm1Sesh related

Antonopoulos C; Cumberbatch M; Dearman RJ; Daniel RJ; Kimber I; Groves RW. 2001. Functional caspase-1 is required for Langerhans cell migration and optimal contact sensitization in mice. J Immunol 166(6):3672-7. [PubMed: 11238606]  [MGI Ref ID J:124939]

Boyden ED; Dietrich WF. 2006. Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin Nat Genet 38(2):240-244. [PubMed: 16429160]  [MGI Ref ID J:99748]

Chamberlain J; Evans D; King A; Dewberry R; Dower S; Crossman D; Francis S. 2006. Interleukin-1beta and signaling of interleukin-1 in vascular wall and circulating cells modulates the extent of neointima formation in mice. Am J Pathol 168(4):1396-403. [PubMed: 16565512]  [MGI Ref ID J:107324]

Cheng W; Shivshankar P; Li Z; Chen L; Yeh IT; Zhong G. 2008. Caspase-1 contributes to Chlamydia trachomatis-induced upper urogenital tract inflammatory pathologies without affecting the course of infection. Infect Immun 76(2):515-22. [PubMed: 18025098]  [MGI Ref ID J:130235]

Cumberbatch M; Dearman RJ; Antonopoulos C; Groves RW; Kimber I. 2001. Interleukin (IL)-18 induces Langerhans cell migration by a tumour necrosis factor-alpha- and IL-1beta-dependent mechanism. Immunology 102(3):323-30. [PubMed: 11298831]  [MGI Ref ID J:68644]

Edelson BT; Unanue ER. 2002. MyD88-dependent but Toll-like receptor 2-independent innate immunity to Listeria: no role for either in macrophage listericidal activity. J Immunol 169(7):3869-75. [PubMed: 12244184]  [MGI Ref ID J:120406]

Feliciani C; Toto P; Amerio P; Pour SM; Coscione G; Shivji G; Wang B; Sauder DN. 2000. In vitro and in vivo expression of interleukin-1alpha and tumor necrosis factor-alpha mRNA in pemphigus vulgaris: interleukin-1alpha and tumor necrosis factor-alpha are involved in acantholysis. J Invest Dermatol 114(1):71-7. [PubMed: 10620118]  [MGI Ref ID J:127060]

Gehrig A; Janssen A; Horling F; Grimm C; Weber BH. 2006. The role of caspases in photoreceptor cell death of the retinoschisin-deficient mouse. Cytogenet Genome Res 115(1):35-44. [PubMed: 16974082]  [MGI Ref ID J:112879]

Henry T; Brotcke A; Weiss DS; Thompson LJ; Monack DM. 2007. Type I interferon signaling is required for activation of the inflammasome during Francisella infection. J Exp Med 204(5):987-94. [PubMed: 17452523]  [MGI Ref ID J:125737]

Jolicoeur P; Hu C; Mak TW; Martinou JC; Kay DG. 2003. Protection against murine leukemia virus-induced spongiform myeloencephalopathy in mice overexpressing Bcl-2 but not in mice deficient for interleukin-6, inducible nitric oxide synthetase, ICE, Fas, Fas ligand, or TNF-R1 genes. J Virol 77(24):13161-70. [PubMed: 14645573]  [MGI Ref ID J:86761]

Kang TJ; Basu S; Zhang L; Thomas KE; Vogel SN; Baillie L; Cross AS. 2008. Bacillus anthracis spores and lethal toxin induce IL-1beta via functionally distinct signaling pathways. Eur J Immunol 38(6):1574-84. [PubMed: 18493980]  [MGI Ref ID J:136368]

Li P; Allen H; Banerjee S; Franklin S; Herzog L; Johnston C; McDowell J; Paskind M; Rodman L; Salfeld J; Towne E; Tracey D; Wardwell S; Wei FY; Wong W; Kamen R; Seshadri T. 1995. Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock. Cell 80(3):401-11. [PubMed: 7859282]  [MGI Ref ID J:22964]

Li P; Allen H; Banerjee S; Seshadri T. 1997. Characterization of mice deficient in interleukin-1 beta converting enzyme. J Cell Biochem 64(1):27-32. [PubMed: 9015751]  [MGI Ref ID J:40691]

Liege S; Moze E; Kelley KW; Parnet P; Neveu PJ. 2000. Activation of the hypothalamic-pituitary-adrenal axis in IL-1 beta-converting enzyme-deficient mice. Neuroimmunomodulation 7(4):189-94. [PubMed: 10810251]  [MGI Ref ID J:62433]

Lightfield KL; Persson J; Brubaker SW; Witte CE; von Moltke J; Dunipace EA; Henry T; Sun YH; Cado D; Dietrich WF; Monack DM; Tsolis RM; Vance RE. 2008. Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin. Nat Immunol 9(10):1171-8. [PubMed: 18724372]  [MGI Ref ID J:141008]

Liu XH; Kwon D; Schielke GP; Yang GY; Silverstein FS; Barks JD. 1999. Mice deficient in interleukin-1 converting enzyme are resistant to neonatal hypoxic-ischemic brain damage. J Cereb Blood Flow Metab 19(10):1099-108. [PubMed: 10532634]  [MGI Ref ID J:98866]

Mariathasan S; Weiss DS; Dixit VM; Monack DM. 2005. Innate immunity against Francisella tularensis is dependent on the ASC/caspase-1 axis. J Exp Med 202(8):1043-9. [PubMed: 16230474]  [MGI Ref ID J:116821]

Mastronardi C; Whelan F; Yildiz OA; Hannestad J; Elashoff D; McCann SM; Licinio J; Wong ML. 2007. Caspase 1 deficiency reduces inflammation-induced brain transcription. Proc Natl Acad Sci U S A 104(17):7205-10. [PubMed: 17409187]  [MGI Ref ID J:120877]

Meissner F; Molawi K; Zychlinsky A. 2008. Superoxide dismutase 1 regulates caspase-1 and endotoxic shock. Nat Immunol 9(8):866-72. [PubMed: 18604212]  [MGI Ref ID J:137865]

Miggin SM; Palsson-McDermott E; Dunne A; Jefferies C; Pinteaux E; Banahan K; Murphy C; Moynagh P; Yamamoto M; Akira S; Rothwell N; Golenbock D; Fitzgerald KA; O'Neill LA. 2007. NF-kappaB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1. Proc Natl Acad Sci U S A 104(9):3372-7. [PubMed: 17360653]  [MGI Ref ID J:125936]

Miwa K; Asano M; Horai R; Iwakura Y; Nagata S; Suda T. 1998. Caspase 1-independent IL-1beta release and inflammation induced by the apoptosis inducer Fas ligand. Nat Med 4(11):1287-92. [PubMed: 9809553]  [MGI Ref ID J:50775]

Monack DM; Hersh D; Ghori N; Bouley D; Zychlinsky A; Falkow S. 2000. Salmonella exploits caspase-1 to colonize Peyer's patches in a murine typhoid model. J Exp Med 192(2):249-58. [PubMed: 10899911]  [MGI Ref ID J:63488]

Priceputu E; Rodrigue I; Chrobak P; Poudrier J; Mak TW; Hanna Z; Hu C; Kay DG; Jolicoeur P. 2005. The Nef-mediated AIDS-like disease of CD4C/human immunodeficiency virus transgenic mice is associated with increased Fas/FasL expression on T cells and T-cell death but is not prevented in Fas-, FasL-, tumor necrosis factor receptor 1-, or interleukin-1beta-converting enzyme-deficient or Bcl2-expressing transgenic mice. J Virol 79(10):6377-91. [PubMed: 15858021]  [MGI Ref ID J:98353]

Raupach B; Peuschel SK; Monack DM; Zychlinsky A. 2006. Caspase-1-mediated activation of interleukin-1beta (IL-1beta) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection. Infect Immun 74(8):4922-6. [PubMed: 16861683]  [MGI Ref ID J:112400]

Rosenzweig HL; Martin TM; Planck SR; Galster K; Jann MM; Davey MP; Kobayashi K; Flavell RA; Rosenbaum JT. 2008. Activation of NOD2 in vivo induces IL-1beta production in the eye via caspase-1 but results in ocular inflammation independently of IL-1 signaling. J Leukoc Biol 84(2):529-36. [PubMed: 18495787]  [MGI Ref ID J:138433]

Rowe SJ; Allen L; Ridger VC; Hellewell PG; Whyte MK. 2002. Caspase-1-deficient mice have delayed neutrophil apoptosis and a prolonged inflammatory response to lipopolysaccharide-induced acute lung injury. J Immunol 169(11):6401-7. [PubMed: 12444148]  [MGI Ref ID J:80568]

Samardzija M; Wenzel A; Thiersch M; Frigg R; Reme C; Grimm C. 2006. Caspase-1 ablation protects photoreceptors in a model of autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci 47(12):5181-90. [PubMed: 17122101]  [MGI Ref ID J:123100]

Schielke GP; Yang GY; Shivers BD; Betz AL. 1998. Reduced ischemic brain injury in interleukin-1 beta converting enzyme-deficient mice. J Cereb Blood Flow Metab 18(2):180-5. [PubMed: 9469161]  [MGI Ref ID J:46306]

Sundquist M; Wick MJ. 2005. TNF-alpha-dependent and -independent maturation of dendritic cells and recruited CD11c(int)CD11b+ Cells during oral Salmonella infection. J Immunol 175(5):3287-98. [PubMed: 16116221]  [MGI Ref ID J:113214]

Wong ML; Xie B; Beatini N; Phu P; Marathe S; Johns A; Gold PW; Hirsch E; Williams KJ; Licinio J; Tabas I. 2000. Acute systemic inflammation up-regulates secretory sphingomyelinase in vivo: A possible link between inflammatory cytokines and atherogenesis Proc Natl Acad Sci U S A 97(15):8681-6. [PubMed: 10890909]  [MGI Ref ID J:63405]

Xu H; Barks JD; Schielke GP; Silverstein FS. 2001. Attenuation of hypoxia-ischemia-induced monocyte chemoattractant protein-1 expression in brain of neonatal mice deficient in interleukin-1 converting enzyme. Brain Res Mol Brain Res 90(1):57-67. [PubMed: 11376856]  [MGI Ref ID J:69589]

Yang GY; Schielke GP; Gong C; Mao Y; Ge HL; Liu XH; Betz AL. 1999. Expression of tumor necrosis factor-alpha and intercellular adhesion molecule-1 after focal cerebral ischemia in interleukin-1beta converting enzyme deficient mice. J Cereb Blood Flow Metab 19(10):1109-17. [PubMed: 10532635]  [MGI Ref ID J:59704]

Yao JH; Ye SM; Burgess W; Zachary JF; Kelley KW; Johnson RW. 1999. Mice deficient in interleukin-1beta converting enzyme resist anorexia induced by central lipopolysaccharide. Am J Physiol 277(5 Pt 2):R1435-43. [PubMed: 10564217]  [MGI Ref ID J:58677]

Zhang WH; Wang X; Narayanan M; Zhang Y; Huo C; Reed JC; Friedlander RM. 2003. Fundamental role of the Rip2/caspase-1 pathway in hypoxia and ischemia-induced neuronal cell death. Proc Natl Acad Sci U S A 100(26):16012-7. [PubMed: 14663141]  [MGI Ref ID J:88212]

de Bilbao F; Giannakopoulos P; Srinivasan A; Dubois-Dauphin M. 2000. In vivo study of motoneuron death induced by nerve injury in mice deficient in the caspase 1/ interleukin-1 beta-converting enzyme. Neuroscience 98(3):573-83. [PubMed: 10869851]  [MGI Ref ID J:118715]

van der Velden AW; Velasquez M; Starnbach MN. 2003. Salmonella rapidly kill dendritic cells via a caspase-1-dependent mechanism. J Immunol 171(12):6742-9. [PubMed: 14662878]  [MGI Ref ID J:118499]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	A footpad injection of Complete Freund s Adjuvant (CFA) administered once at weaning will delay diabetes onset, thus extending the lifespan of breeders. Use of Complete Freund s Adjuvant in NOD mice can be found in Current Protocols in Immunology page 15.9.19, Reproduction.
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 Type 1 Diabetes Repository collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	001976 NOD/ShiLtJ
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

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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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