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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID 		Casp1tm1Sesh
targeted mutation 1, Tara Seshadri
MGI:1927822
Summary 13 genotypes


Genotype
MGI:3581549
cx1
Allelic
Composition		 Casp1tm1Sesh/Casp1tm1Sesh
Casp4del/Casp4del
Genetic
Background		 B10.Cg-Casp1tm1Sesh Casp4del H2r H2-T18b
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1tm1Sesh mutation (5 available); any Casp1 mutation (41 available)
Casp4del mutation (4 available); any Casp4 mutation (30 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
decreased susceptibility to bacterial infection induced morbidity/mortality ( J:63488 )
• homozygotes exhibit increased resistance to Salmonella infection with an oral S. typhimurium 50% lethal dose (LD50) that is 1,000-fold higher than that of wild-type mice
• following oral infection with an oral dose of S. typhimurium that is 100-fold higher than the LD50 in homozygotes, death occurs about 4 days later relative to wild-type mice

immune system
decreased inflammatory response ( J:63488 )
• following oral infection, Salmonella breachs the M cell barrier of mutant mice efficiently; however, homozygotes show a significant reduction in the number of intracellular bacteria and the recruitment of polymorphonuclear lymphocytes in Peyer's patches relative to wild-type mice
• in vitro, mutant macrophages are not inherently different in their capacity to kill Salmonella relative to wild-type-derived macrophages
decreased susceptibility to bacterial infection ( J:63488 )
• following oral infection, Salmonella fails disseminate systemically with significantly reduced colonization in the Peyer's patches, mesenteric lymph nodes, and spleens after an oral dose of S. typhimurium that is 100-fold higher than the LD50; in homozygotes, death occurs about 4 days later relative to wild-type mice
• notably, homozygotes and wild-type mice are equally susceptible to intraperitoneally injected Salmonella (100 SL1344 bacteria), exhibiting comparable spleen colonization and mortality
• in addition, homozygotes and wild-type are equally susceptible to colonization by Yersinia pseudotuberculosis, another enteric pathogen that normally invades the Peyer's patches
decreased susceptibility to bacterial infection induced morbidity/mortality ( J:63488 )
• homozygotes exhibit increased resistance to Salmonella infection with an oral S. typhimurium 50% lethal dose (LD50) that is 1,000-fold higher than that of wild-type mice
• following oral infection with an oral dose of S. typhimurium that is 100-fold higher than the LD50 in homozygotes, death occurs about 4 days later relative to wild-type mice

cellular
decreased apoptosis ( J:63488 )
• after an oral dose of S. typhimurium that is 100-fold higher than the LD50, homozygotes show significantly less apoptotic cells in Peyer's patches (PP); in contrast, increased apoptosis in wild-type PP correlates with colonization




Genotype
MGI:3851239
cx2
Allelic
Composition		 Casp1tm1Sesh/Casp1tm1Sesh
Casp4del/Casp4del
Slc11a1s/Slc11a1s
Genetic
Background		 B6.129S2-Casp1tm1Sesh Casp4del
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1tm1Sesh mutation (5 available); any Casp1 mutation (41 available)
Casp4del mutation (4 available); any Casp4 mutation (30 available)
Slc11a1s mutation (0 available); any Slc11a1 mutation (40 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
abnormal macrophage physiology ( J:112400 )
• macrophages are resistant to cytotoxicity induced by in vitro Salmonella infection
increased susceptibility to bacterial infection ( J:112400 )
• mice succumb more rapidly than controls to 108 CFU of Salmonella with a median survival time of 6 days compared to 8 days for controls
• there is an average 30-fold-higher bacterial loads in infected Peyer's patches, mesenteric lymph nodes, and spleens than in the infected organs of wild-type animals

hematopoietic system
abnormal macrophage physiology ( J:112400 )
• macrophages are resistant to cytotoxicity induced by in vitro Salmonella infection




Genotype
MGI:5468971
cx3
Allelic
Composition		 Casp1tm1Sesh/Casp1tm1Sesh
Casp4del/Casp4del
Genetic
Background		 B6.129S2(NOD)-Casp1tm1Sesh Casp4del
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1tm1Sesh mutation (5 available); any Casp1 mutation (41 available)
Casp4del mutation (4 available); any Casp4 mutation (30 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
decreased susceptibility to xenobiotic induced morbidity/mortality ( J:193522 )
• in response to LPS challenge in a model of acute septic shock

immune system
decreased macrophage apoptosis ( J:193522 )
• impaired cell death in response to ATP, Clostridium difficile toxin B, CTB and E. coli
decreased circulating interleukin-1 alpha level ( J:193522 )
• in response to LPS challenge in a model of acute septic shock
decreased circulating interleukin-1 beta level ( J:193522 )
• in response to LPS challenge in a model of acute septic shock
decreased circulating interleukin-18 level ( J:193522 )
• in response to LPS challenge in a model of acute septic shock
decreased interleukin-1 alpha secretion ( J:193522 )
• from LPS-primed bone marrow-derived macrophage in response to ATP, C. difficile, CTB and E. coli
decreased interleukin-1 beta secretion ( J:193522 )
• LPS-primed bone marrow-derived macrophages fail to produce IL1b and IL18 in response to ATP, Clostridium difficile toxin B, cholera toxin B (CTB) or E. coli unlike controls
decreased interleukin-18 secretion ( J:193522 )
• LPS-primed bone marrow-derived macrophages fail to produce IL1b and IL18 in response to ATP, Clostridium difficile toxin B, cholera toxin B (CTB) or E. coli unlike controls
decreased susceptibility to endotoxin shock ( J:193522 )
• mice are resistant to LPS challenge in a model of acute septic shock with reduced mortality and serum levels of IL1b, IL1a and IL18

cellular
decreased apoptosis ( J:243487 )
• of intestinal epithelial cells (IECs) after oral rotavirus inoculation of 8 day old pups
decreased macrophage apoptosis ( J:193522 )
• impaired cell death in response to ATP, Clostridium difficile toxin B, CTB and E. coli

homeostasis/metabolism
decreased circulating interleukin-1 alpha level ( J:193522 )
• in response to LPS challenge in a model of acute septic shock
decreased circulating interleukin-1 beta level ( J:193522 )
• in response to LPS challenge in a model of acute septic shock
decreased circulating interleukin-18 level ( J:193522 )
• in response to LPS challenge in a model of acute septic shock
decreased susceptibility to xenobiotic induced morbidity/mortality ( J:193522 )
• in response to LPS challenge in a model of acute septic shock

hematopoietic system
decreased macrophage apoptosis ( J:193522 )
• impaired cell death in response to ATP, Clostridium difficile toxin B, CTB and E. coli




Genotype
MGI:4839936
cx4
Allelic
Composition		 Casp1tm1Sesh/Casp1tm1Sesh
Casp4del/Casp4del
Genetic
Background		 C3.129S2-Casp1tm1Sesh Casp4del
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1tm1Sesh mutation (5 available); any Casp1 mutation (41 available)
Casp4del mutation (4 available); any Casp4 mutation (30 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
increased susceptibility to bacterial infection induced morbidity/mortality ( J:136368 )
• following infection with Sterne 34F2 strain of Bacillus anthracis

immune system
abnormal macrophage physiology ( J:136368 )
• macrophages exhibit impaired ability to kill Bacillus anthracis compared with wild-type cells
decreased interleukin-1 beta secretion ( J:136368 )
• following exposure of macrophages to LPS or Bacillus anthracis spores
increased susceptibility to bacterial infection ( J:136368 )
• following infection with Sterne 34F2 strain of Bacillus anthracis, mice exhibit increased mortality and reduced clearing compared with similarly treated wild-type mice
increased susceptibility to bacterial infection induced morbidity/mortality ( J:136368 )
• following infection with Sterne 34F2 strain of Bacillus anthracis

hematopoietic system
abnormal macrophage physiology ( J:136368 )
• macrophages exhibit impaired ability to kill Bacillus anthracis compared with wild-type cells




Genotype
MGI:3581548
cx5
Allelic
Composition		 Casp1tm1Sesh/Casp1tm1Sesh
Casp4del/Casp4del
Genetic
Background		 C3N.129S2-Casp1tm1Sesh Casp4del
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1tm1Sesh mutation (5 available); any Casp1 mutation (41 available)
Casp4del mutation (4 available); any Casp4 mutation (30 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
abnormal response to infection ( J:86761 )
• following inoculation with neurovirulent ts-1 MuLV, both homozygotes and their respective control heterozygote littermates develop hind limb paralysis with comparable latencies and spongiform lesions of comparable severity
• lack of protection from MuLV-induced neurodegeneration suggests that pathways of neuronal cell death induced by ts-1 MuLV and hypoxia or ischemia are not identical




Genotype
MGI:4360918
cx6
Allelic
Composition		 Casp1tm1Sesh/Casp1tm1Sesh
Casp4del/Casp4del
Genetic
Background		 involves: 129 * 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1tm1Sesh mutation (5 available); any Casp1 mutation (41 available)
Casp4del mutation (4 available); any Casp4 mutation (30 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
decreased interleukin-1 beta secretion ( J:50775 )
• freshly isolated peritoneal exudate cells (neutrophils and B cells) secrete less IL-1beta in response to LPS than in controls
• IL-1beta response to soluble FasL is similar to controls




Genotype
MGI:3696112
cx7
Allelic
Composition		 Casp1tm1Sesh/Casp1+
Casp4del/Casp4+
Genetic
Background		 involves: 129S1/SvImJ * 129S2/SvPas * NOD
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1tm1Sesh mutation (5 available); any Casp1 mutation (41 available)
Casp4del mutation (4 available); any Casp4 mutation (30 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
abnormal macrophage physiology ( J:99748 )
• Casp1-deficient bone marrow-derived macrophages that are homozygous for the 129S1 Nlrp1b transgene are highly resistant to necrosis induced by B. antracis lethal toxin (LeTx) while Casp1-heterozygous mice that are homozygous for the 129S1 Nlrp1b allele show a high susceptibility to necrosis from LeTx

hematopoietic system
abnormal macrophage physiology ( J:99748 )
• Casp1-deficient bone marrow-derived macrophages that are homozygous for the 129S1 Nlrp1b transgene are highly resistant to necrosis induced by B. antracis lethal toxin (LeTx) while Casp1-heterozygous mice that are homozygous for the 129S1 Nlrp1b allele show a high susceptibility to necrosis from LeTx




Genotype
MGI:5474285
cx8
Allelic
Composition		 Casp1tm1Sesh/Casp1tm1Sesh
Nlrp1aNeut1/Nlrp1aNeut1
Genetic
Background		 involves: 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1tm1Sesh mutation (5 available); any Casp1 mutation (41 available)
Nlrp1aNeut1 mutation (0 available); any Nlrp1a mutation (64 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
immune system phenotype ( J:191055 )
N
• no neutrophilia or inflammatory disease
• no loss of macrophage progenitor cells

homeostasis/metabolism




Genotype
MGI:3574069
cx9
Allelic
Composition		 Casp1tm1Sesh/Casp1+
Casp4del/Casp4+
Genetic
Background		 involves: 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1tm1Sesh mutation (5 available); any Casp1 mutation (41 available)
Casp4del mutation (4 available); any Casp4 mutation (30 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
decreased interleukin-1 beta secretion ( J:22964 )
• heterozygotes are slightly impaired in their capacity to produce mature IL-1beta: ex vivo, heterozygous peritoneal macrophages stimulated with LPS and ATP release 50% of wild-type IL-1beta levels
• no decrease in pro-IL-1beta synthesis or release is detected




Genotype
MGI:3574053
cx10
Allelic
Composition		 Casp1tm1Sesh/Casp1tm1Sesh
Casp4del/Casp4del
Genetic
Background		 involves: 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1tm1Sesh mutation (5 available); any Casp1 mutation (41 available)
Casp4del mutation (4 available); any Casp4 mutation (30 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
neoplasm
neoplasm ( J:22964 , J:40691 )
N
• homozygotes are viable and healthy with no signs of histological abnormalities in major organs; no spontaneous tumors are detected until the age of 25 weeks (J:22964)
• homozygotes remain tumor-free at the age of 18 months (J:40691)

cellular
cellular phenotype ( J:22964 , J:40691 )
N
• macrophages and thymocytes from mutant mice retain their capacity to undergo apoptosis upon ex vivo stimulation by several different signals (J:22964)
• in response to ATP, mutant peritoneal macrophages undergo normal apoptosis relative to wild-type (J:40691)
• in response to dexamethasone, aging or gamma irradiation, thymocytes from young homozygotes undergo normal apoptosis relative to wild-type (J:40691)
• in response to LPS and D-galactosamine, homozygotes undergo normal TNF-induced hepatocyte apoptosis and show normal kinetics of death from hepatic failure relative to wild-type mice (J:40691)
abnormal apoptosis ( J:80568 )
• mutant peripheral blood neutrophils display retarded constitutive apoptosis relative to wild-type neutrophils
• mutant peripheral blood neutrophils show no LPS-mediated inhibition of apoptosis but remain susceptible to Fas-mediated apoptosis
decreased T cell apoptosis ( J:40691 )
• in vitro, thymocytes from young homozygotes are resistant to Fas-induced apoptosis as measured by cell viability
decreased neuron apoptosis ( J:88212 )
• cultured cerebrocortical neurons from homozygotes are highly resistant to oxygen/glucose deprivation (OGD)-induced neuronal cell death, showing only 50% of lactate dehydrogenase release relative to wild-type neurons
• also, mutant neurons are highly resistant to Ripk2-mediated cell death; transfecting caspase-1 into mutant neurons restores sensitivity to Ripk2-induced apoptosis
• notably, cultured neurons show inhibition of OGD-mediated processing of various members of the caspase pathway, cleavage of Bid, and hypoxia-associated loss of mitochondrial transmembrane potential; in vivo, these findings are confirmed in a cerebral ischemia model
abnormal cell migration ( J:68644 )
• in homozygotes lacking bioactive IL-1beta, IL-18 fails to induce the expected migration of epidermal Langerhans cells to draining lymph nodes following skin sensitization; as a result, immunostimulatory dendritic cells fail to accumulate in regional lymph nodes resulting in impaired initiation of cutaneous immune responses

hematopoietic system
hematopoietic system phenotype ( J:22964 )
N
• homozygotes exhibit normal numbers of leukocytes, erythrocytes, and platelets in peripheral blood
• freshly isolated mutant thymuses, spleens and lymph nodes contain a normal % of various T cell subsets and B cells relative to wild-type
decreased T cell apoptosis ( J:40691 )
• in vitro, thymocytes from young homozygotes are resistant to Fas-induced apoptosis as measured by cell viability
abnormal neutrophil physiology ( J:80568 )
• in addition to delayed apoptosis, mutant neutrophils show absence of LPS-stimulated IL-1beta production relative to wild-type
• in response to LPS-mediated acute lung injury, homozygotes show significantly increased total and percent neutrophil counts at 24 and 48 h; however, these numbers decline to wild-type levels by 72 h suggesting a delay in inflammatory neutrophil apoptosis
abnormal macrophage physiology ( J:22964 )
• ex vivo, thioglycollate-elicited peritoneal macrophages stimulated with LPS and ATP are defective in IL-1beta processing and release

immune system
immune system phenotype ( J:40691 )
N
• in homozygotes, the % of B lymphocytes and the various T lymphocyte subsets found in mutant thymuses, spleens and lymph nodes appear unaffected relative to wild-type
• the size and lymphocyte counts in these lymphoid organs appear normal; myeolopoiesis remains unaffected
decreased T cell apoptosis ( J:40691 )
• in vitro, thymocytes from young homozygotes are resistant to Fas-induced apoptosis as measured by cell viability
abnormal neutrophil physiology ( J:80568 )
• in addition to delayed apoptosis, mutant neutrophils show absence of LPS-stimulated IL-1beta production relative to wild-type
• in response to LPS-mediated acute lung injury, homozygotes show significantly increased total and percent neutrophil counts at 24 and 48 h; however, these numbers decline to wild-type levels by 72 h suggesting a delay in inflammatory neutrophil apoptosis
abnormal macrophage physiology ( J:22964 )
• ex vivo, thioglycollate-elicited peritoneal macrophages stimulated with LPS and ATP are defective in IL-1beta processing and release
decreased circulating interleukin-1 alpha level ( J:22964 )
• LPS-treated mice show a 5-fold decrease in IL-1alpha levels in vivo
decreased circulating interleukin-1 beta level ( J:22964 )
• in vivo, homozygous males injected with a high dose of LPS display undetectable levels of mature IL-1beta in their plasma; females are slightly less affected
decreased circulating interleukin-6 level ( J:22964 )
• after injection with a high dose of LPS, homozygotes display a moderate reduction in IL-6 levels relative to wild-type mice
decreased circulating tumor necrosis factor level ( J:22964 )
• after injection with a high dose of LPS, homozygotes display a moderate reduction in TNF levels relative to wild-type mice
decreased interleukin-1 alpha secretion ( J:22964 )
• surprisingly, homozygous males are also defective in IL-1alpha production, with macrophages releasing only 20-25% of wild-type IL-1alpha levels after stimulation with LPS and ATP ex vivo
decreased interleukin-1 beta secretion ( J:22964 , J:88212 )
• homozygotes are impaired in their capacity to produce mature IL-1beta (J:22964)
• ex vivo, mutant peritoneal macrophages stimulated with LPS and ATP release less that 1% of wild-type IL-1beta levels; however, no decrease in pro-IL-1beta synthesis or release is detected (J:22964)
• in culture, mutant cortical neurons exhibit inhibition of hypoxia-mediated generation of mature IL-1beta (J:88212)
abnormal inflammatory response ( J:80568 )
• in response to LPS-mediated acute lung injury, homozygotes exhibit a prolonged neutrophilic inflammatory response and evidence of caspase-1-independent IL-1beta production in the lung
decreased susceptibility to endotoxin shock ( J:22964 , J:40691 )
• strikingly, homozygotes are significantly resistant to the lethal effects of endotoxic shock after a high dose of LPS (J:22964)
• whereas all LPS-treated wild-type mice die within 30 hours after injection, all homozygotes survive for >45 hours, with only 30% of mutants dying during the next 5 days (J:22964)

reproductive system
reproductive system phenotype ( J:22964 , J:40691 )
N
• homozygotes are fertile and produce a normal litter size relative to wild-type (J:22964)
• in addition, post-lactation involution of mammary glands remains grossly normal in mutant post-partum females (J:22964)
(J:40691)

nervous system
decreased neuron apoptosis ( J:88212 )
• cultured cerebrocortical neurons from homozygotes are highly resistant to oxygen/glucose deprivation (OGD)-induced neuronal cell death, showing only 50% of lactate dehydrogenase release relative to wild-type neurons
• also, mutant neurons are highly resistant to Ripk2-mediated cell death; transfecting caspase-1 into mutant neurons restores sensitivity to Ripk2-induced apoptosis
• notably, cultured neurons show inhibition of OGD-mediated processing of various members of the caspase pathway, cleavage of Bid, and hypoxia-associated loss of mitochondrial transmembrane potential; in vivo, these findings are confirmed in a cerebral ischemia model
decreased susceptibility to ischemic brain injury ( J:69589 , J:98866 )
• under mild lesioning conditions (right carotid ligation plus 40 min 10% O2), newborn homozygotes show attenuated hypoxia-ischemia induced CCL2 (chemokine (C-C motif) ligand 2; also, MCP-1) expression at 8 h post-hypoxia relative to wild-type; no genotype differences in CCL2 production are observed in animals undergoing longer periods of hypoxia-ischemia (severe insult) (J:69589)
• following right carotid artery ligation, newborn homozygotes (P9-P10) are resistant to moderate, but not to severe cerebral hypoxic-ischemic insults relative to wild-type mice (J:98866)

homeostasis/metabolism
decreased circulating interleukin-1 alpha level ( J:22964 )
• LPS-treated mice show a 5-fold decrease in IL-1alpha levels in vivo
decreased circulating interleukin-1 beta level ( J:22964 )
• in vivo, homozygous males injected with a high dose of LPS display undetectable levels of mature IL-1beta in their plasma; females are slightly less affected
decreased circulating interleukin-6 level ( J:22964 )
• after injection with a high dose of LPS, homozygotes display a moderate reduction in IL-6 levels relative to wild-type mice
decreased circulating tumor necrosis factor level ( J:22964 )
• after injection with a high dose of LPS, homozygotes display a moderate reduction in TNF levels relative to wild-type mice
decreased susceptibility to ischemic brain injury ( J:69589 , J:98866 )
• under mild lesioning conditions (right carotid ligation plus 40 min 10% O2), newborn homozygotes show attenuated hypoxia-ischemia induced CCL2 (chemokine (C-C motif) ligand 2; also, MCP-1) expression at 8 h post-hypoxia relative to wild-type; no genotype differences in CCL2 production are observed in animals undergoing longer periods of hypoxia-ischemia (severe insult) (J:69589)
• following right carotid artery ligation, newborn homozygotes (P9-P10) are resistant to moderate, but not to severe cerebral hypoxic-ischemic insults relative to wild-type mice (J:98866)

cardiovascular system
cardiovascular system phenotype ( J:107324 )
N
• mice exhibit normal response to carotid ligation




Genotype
MGI:5468972
cx11
Allelic
Composition		 Casp1tm1Sesh/Casp1tm1Sesh
Casp4del/Casp4del
Tg(Casp4)#Gne/0
Genetic
Background		 involves: 129S2/SvPas * C57BL/6 * NOD/ShiLtJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1tm1Sesh mutation (5 available); any Casp1 mutation (41 available)
Casp4del mutation (4 available); any Casp4 mutation (30 available)
Tg(Casp4)#Gne mutation (0 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
decreased macrophage apoptosis ( J:193522 )
• impaired cell death in response to ATP and Clostridium difficile toxin B
decreased circulating interleukin-1 beta level ( J:193522 )
• in response to LPS challenge in a model of acute septic shock
decreased circulating interleukin-18 level ( J:193522 )
• in response to LPS challenge in a model of acute septic shock
decreased interleukin-1 alpha secretion ( J:193522 )
• from LPS-primed bone marrow-derived macrophage in response to ATP and C. difficile
• however, IL1a secretion is restored in response to CTB and E. coli
decreased interleukin-1 beta secretion ( J:193522 )
• LPS-primed bone marrow-derived macrophages fail to produce IL1b and IL18 in response to ATP, Clostridium difficile toxin B, cholera toxin B (CTB) or E. coli unlike controls
decreased interleukin-18 secretion ( J:193522 )
• LPS-primed bone marrow-derived macrophages fail to produce IL1b and IL18 in response to ATP, Clostridium difficile toxin B, cholera toxin B (CTB) or E. coli unlike controls
decreased susceptibility to endotoxin shock ( J:193522 )
• mice treated with LPS challenge in a model of acute septic shock exhibit reduced serum levels of IL1b and IL18 compared with controls
• however, mice do not survive beyond 26 hours and serum levels of IL1a are increased

homeostasis/metabolism
decreased circulating interleukin-1 beta level ( J:193522 )
• in response to LPS challenge in a model of acute septic shock
decreased circulating interleukin-18 level ( J:193522 )
• in response to LPS challenge in a model of acute septic shock

cellular
decreased macrophage apoptosis ( J:193522 )
• impaired cell death in response to ATP and Clostridium difficile toxin B

hematopoietic system
decreased macrophage apoptosis ( J:193522 )
• impaired cell death in response to ATP and Clostridium difficile toxin B




Genotype
MGI:3851240
cx12
Allelic
Composition		 Casp1tm1Sesh/Casp1tm1Sesh
Casp4del/Casp4del
Slc11a1r/Slc11a1s
Genetic
Background		 involves: 129/Sv * 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1tm1Sesh mutation (5 available); any Casp1 mutation (41 available)
Casp4del mutation (4 available); any Casp4 mutation (30 available)
Slc11a1r mutation (2 available); any Slc11a1 mutation (40 available)
Slc11a1s mutation (0 available); any Slc11a1 mutation (40 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
increased susceptibility to bacterial infection ( J:112400 )
• mice succumb to 2x1010 CFU Salmonella infection with a median survival of 20 days compared to no death by infection for the control mice




Genotype
MGI:3581521
cx13
Allelic
Composition		 Casp1tm1Sesh/Casp1tm1Sesh
Casp4del/Casp4del
Genetic
Background		 NOD.129S2(B6)-Casp1tm1Sesh Casp4del/LtJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1tm1Sesh mutation (5 available); any Casp1 mutation (41 available)
Casp4del mutation (4 available); any Casp4 mutation (30 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
decreased interleukin-1 alpha secretion ( 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 ( 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 ( 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
homeostasis/metabolism phenotype ( J:87250 )
N
• 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

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
type 1 diabetes mellitus DOID:9744 OMIM:222100
 J:87250




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Send questions and comments to User Support. 		last database update
04/23/2024
MGI 6.23 		The Jackson Laboratory