Former Names NOD.129S2(B6)-Casp1tm1Sesh/LtJ (Changed: 24-APR-13 ) Type Deletion; Additional information on Mice with Chromosomal Aberrations. Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote (Female x Male) 01-MAR-06 Species laboratory mouse Background Strain NOD/ShiLt Donor Strain 129S2 Generation [N10F13p]+F16N1F6 (29-JUN-11)
Generation DefinitionsDonating Investigator Dr. Edward Leiter, The Jackson Laboratory Appearance
albino, pink-eyed
Related Genotype: A/? Tyrc/TyrcDescription
Casp1tm1Sesh 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)- Casp1tm1Sesh /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 Casp1tm1Sesh deficient animals is equivalent to NOD/Lt, heterozygote and wild-type controls. Weanling Casp1tm1Sesh 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)- Casp1tm1Sesh/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-Casp1tm1Sesh 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)- Casp1tm1Sesh /LtJ homozygous strain at N10F11 was transferred from Edward Leiter's research colony to a Jackson Laboratory distribution colony.
| Control | ||
|---|---|---|
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
Strains carrying Casp1tm1Sesh allele
005346 NOD.Cg-Il10tm1Cgn Casp1tm1Sesh Casp4del/LtJ View Strains carrying Casp1tm1Sesh (1 strain)
Strains carrying Casp4del allele
005346 NOD.Cg-Il10tm1Cgn Casp1tm1Sesh Casp4del/LtJ View Strains carrying Casp4del (1 strain)
Strains carrying other alleles of Casp1
016621 B6N.129S2-Casp1tm1Flv/J View Strains carrying other alleles of Casp1 (1 strain)
View Phenotypic Data
Phenotypic Data
Mouse Phenome Database
View Related Disease (OMIM) Terms
Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).
Diabetes Mellitus, Insulin-Dependent; IDDM
View Mammalian Phenotype Terms
Mammalian Phenotype Terms provided by MGI
assigned by genotype
Casp1tm1Sesh/Casp1tm1Sesh Casp4del/Casp4del
NOD.129S2(B6)-Casp1tm1Sesh Casp4del/LtJ
- immune system phenotype
- decreased interleukin-1 alpha secretion
- 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 (MGI Ref ID J:87250)
- decreased interleukin-1 beta secretion
- 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 (MGI Ref ID J:87250)
- decreased interleukin-18 secretion
- cultured LPS-stimulated bone marrow derived macrophages from homozygotes produce no immunoreactive IL18 relative to heterozygous or wild-type (NOD/Lt) mice (MGI Ref ID J:87250)
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype
- homozygotes show no significant differences in the rate or in total incidence of diabetes relative to heterozygotes or wild-type (NOD/Lt) control mice (MGI Ref ID J:87250)
- 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 (MGI Ref ID J:87250)
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:Casp1tm1Sesh related
Diabetes and Obesity Research
Type 1 Diabetes (IDDM)
Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
B cell defects
Research Tools
Diabetes and Obesity Research
| Allele Symbol | Casp1tm1Sesh | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Tara Seshadri | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Casp1 -; Casp1-/Casp11129mt; Caspase-1-; ICE -; casp-1-; | ||
| Mutation Made By | Dr. 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; | ||
| General Note | The ES cells used to generate this allele contain the linked Casp4del truncated allele that fails to produce a functional Casp4. Phenotypes associated with this allele may be affected by the presence of the Caspdel allele. J:193522 | ||
| 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. This allele was generated in ES cells that lack protein expression of Casp11 (Casp129mt). [MGI Ref ID J:22964] | ||
| Allele Symbol | Casp4del | ||
| Allele Name | deletion | ||
| Allele Type | Spontaneous | ||
| Common Name(s) | Casp129; | ||
| Strain of Origin | 129P3/J and 129S1/SvImJ and 129S2/SvPas and 129S6/SvEvTac and 129X1/SvJ | ||
| Gene Symbol and Name | Casp4, caspase 4, apoptosis-related cysteine peptidase | ||
| Chromosome | 9 | ||
| Gene Common Name(s) | Casp11; Caspase-11; ICE(rel)II; ICEREL-II; ICH-2; Mih1/TX; TX; capase 11, apoptosis-related cysteine protease; caspase 11, apoptosis-related cysteine peptidase; ich-3; | ||
| Molecular Note | RT-PCR confirmed that five 129 substrains (129X1/SvJ, 129S1/SvImJ, 129S2/SvPas, 129S6/SvEvTac and 129P3/J) express a transcript that lacks exon 7 (delta110 isoform). Sequencing identified a 5 bp deletion in exon 7 that results in the fusion of exon 6 and8, a frame-shift after proline 304 and a stop codon after 5 aberrant amino acids. This deletion is not present in C57BL/6. Western blot analysis confirmed the absence of protein expression in LPS-primed macrophage. [MGI Ref ID J:193522] | ||
Genotyping Protocols
Casp1tm1Sesh, Fast MCA
Casp1tm1Sesh, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
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Antonopoulos C; Cumberbatch M; Mee JB; Dearman RJ; Wei XQ; Liew FY; Kimber I; Groves RW. 2008. IL-18 is a key proximal mediator of contact hypersensitivity and allergen-induced Langerhans cell migration in murine epidermis. J Leukoc Biol 83(2):361-7. [PubMed: 17984289] [MGI Ref ID J:145093]
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Dewamitta SR; Nomura T; Kawamura I; Hara H; Tsuchiya K; Kurenuma T; Shen Y; Daim S; Yamamoto T; Qu H; Sakai S; Xu Y; Mitsuyama M. 2010. Listeriolysin O-dependent bacterial entry into the cytoplasm is required for calpain activation and interleukin-1 alpha secretion in macrophages infected with Listeria monocytogenes. Infect Immun 78(5):1884-94. [PubMed: 20194588] [MGI Ref ID J:160087]
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Gross O; Poeck H; Bscheider M; Dostert C; Hannesschlager N; Endres S; Hartmann G; Tardivel A; Schweighoffer E; Tybulewicz V; Mocsai A; Tschopp J; Ruland J. 2009. Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature 459(7245):433-6. [PubMed: 19339971] [MGI Ref ID J:148538]
Hanley PJ; Kronlage M; Kirschning C; del Rey A; Di Virgilio F; Leipziger J; Chessell IP; Sargin S; Filippov MA; Lindemann O; Mohr S; Konigs V; Schillers H; Bahler M; Schwab A. 2012. Transient P2X7 receptor activation triggers macrophage death independent of Toll-like receptors 2 and 4, caspase-1, and pannexin-1 proteins. J Biol Chem 287(13):10650-63. [PubMed: 22235111] [MGI Ref ID J:183298]
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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]
Kayagaki N; Warming S; Lamkanfi M; Vande Walle L; Louie S; Dong J; Newton K; Qu Y; Liu J; Heldens S; Zhang J; Lee WP; Roose-Girma M; Dixit VM. 2011. Non-canonical inflammasome activation targets caspase-11. Nature 479(7371):117-21. [PubMed: 22002608] [MGI Ref ID J:193522]
Kordes M; Matuschewski K; Hafalla JC. 2011. Caspase-1 Activation of Interleukin-1{beta} (IL-1{beta}) and IL-18 Is Dispensable for Induction of Experimental Cerebral Malaria. Infect Immun 79(9):3633-41. [PubMed: 21708993] [MGI Ref ID J:175707]
Leibundgut-Landmann S; Weidner K; Hilbi H; Oxenius A. 2011. Nonhematopoietic cells are key players in innate control of bacterial airway infection. J Immunol 186(5):3130-7. [PubMed: 21270399] [MGI Ref ID J:169394]
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]
Lichtnekert J; Kulkarni OP; Mulay SR; Rupanagudi KV; Ryu M; Allam R; Vielhauer V; Muruve D; Lindenmeyer MT; Cohen CD; Anders HJ. 2011. Anti-GBM Glomerulonephritis Involves IL-1 but Is Independent of NLRP3/ASC Inflammasome-Mediated Activation of Caspase-1. PLoS One 6(10):e26778. [PubMed: 22046355] [MGI Ref ID J:178074]
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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]
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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]
Serbina NV; Hohl TM; Cherny M; Pamer EG. 2009. Selective expansion of the monocytic lineage directed by bacterial infection. J Immunol 183(3):1900-10. [PubMed: 19596996] [MGI Ref ID J:151581]
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Tang H; Cao W; Kasturi SP; Ravindran R; Nakaya HI; Kundu K; Murthy N; Kepler TB; Malissen B; Pulendran B. 2010. The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling. Nat Immunol 11(7):608-17. [PubMed: 20495560] [MGI Ref ID J:161857]
Trunk G; Oxenius A. 2012. Innate instruction of CD4+ T cell immunity in respiratory bacterial infection. J Immunol 189(2):616-28. [PubMed: 22723524] [MGI Ref ID J:189793]
Vladimer GI; Weng D; Paquette SW; Vanaja SK; Rathinam VA; Aune MH; Conlon JE; Burbage JJ; Proulx MK; Liu Q; Reed G; Mecsas JC; Iwakura Y; Bertin J; Goguen JD; Fitzgerald KA; Lien E. 2012. The NLRP12 inflammasome recognizes Yersinia pestis. Immunity 37(1):96-107. [PubMed: 22840842] [MGI Ref ID J:187388]
Wickstrum JR; Bokhari SM; Fischer JL; Pinson DM; Yeh HW; Horvat RT; Parmely MJ. 2009. Francisella tularensis induces extensive caspase-3 activation and apoptotic cell death in the tissues of infected mice. Infect Immun 77(11):4827-36. [PubMed: 19703976] [MGI Ref ID J:154196]
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Animal Health Reports
Room Number AX11
Colony Maintenance
Mating System Homozygote x Homozygote (Female x Male) 01-MAR-06 Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $195.00 Female or Male Homozygous for Casp1tm1Sesh, Homozygous for Casp4del
Price per Pair (US dollars $) Pair Genotype $390.00 Homozygous for Casp1tm1Sesh, Homozygous for Casp4del x Homozygous for Casp1tm1Sesh, Homozygous for Casp4del 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 |
|
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $253.50 Female or Male Homozygous for Casp1tm1Sesh, Homozygous for Casp4del
Price per Pair (US dollars $) Pair Genotype $507.00 Homozygous for Casp1tm1Sesh, Homozygous for Casp4del x Homozygous for Casp1tm1Sesh, Homozygous for Casp4del 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.
|
|
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 | ||
|---|---|---|
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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