All Phenotypes Casp4<del> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del	B10.Cg-Casp1^tm1Sesh Casp4^del H2^r H2-T18^b	MGI:3581549
cx2	Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del Slc11a1^s/Slc11a1^s	B6.129S2-Casp1^tm1Flv	MGI:3722759
cx3	Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del	B6.129S2-Casp1^tm1Flv	MGI:3711186
cx4	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del Slc11a1^s/Slc11a1^s	B6.129S2-Casp1^tm1Sesh Casp4^del	MGI:3851239
cx5	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del	B6.129S2(NOD)-Casp1^tm1Sesh Casp4^del	MGI:5468971
cx6	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del	C3.129S2-Casp1^tm1Sesh Casp4^del	MGI:4839936
cx7	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del	C3N.129S2-Casp1^tm1Sesh Casp4^del	MGI:3581548
cx8	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del	involves: 129 * 129S2/SvPas * C57BL/6	MGI:4360918
cx9	Casp1^tm1Sesh/Casp1⁺ Casp4^del/Casp4⁺	involves: 129S1/SvImJ * 129S2/SvPas * NOD	MGI:3696112
cx10	Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del Slc11a1^r/Slc11a1^r	involves: 129S2/SvPas	MGI:3722760
cx11	Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del	involves: 129S2/SvPas	MGI:4839914
cx12	Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del Il1r1^tm1Imx/Il1r1^tm1Imx	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	MGI:2179470
cx13	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del	involves: 129S2/SvPas * C57BL/6	MGI:3574053
cx14	Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del	involves: 129S2/SvPas * C57BL/6	MGI:2179469
cx15	Casp1^tm1Sesh/Casp1⁺ Casp4^del/Casp4⁺	involves: 129S2/SvPas * C57BL/6	MGI:3574069
cx16	Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del	involves: 129S2/SvPas * C57BL/6J	MGI:5467384
cx17	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del Tg(Casp4)#Gne/0	involves: 129S2/SvPas * C57BL/6 * NOD/ShiLtJ	MGI:5468972
cx18	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del Slc11a1^r/Slc11a1^s	involves: 129/Sv * 129S2/SvPas * C57BL/6	MGI:3851240
cx19	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del	NOD.129S2(B6)-Casp1^tm1Sesh Casp4^del/LtJ	MGI:3581521

Allelic Composition	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del
Genetic Background	B10.Cg-Casp1^tm1Sesh Casp4^del H2^r H2-T18^b

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♀	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

Allelic Composition	Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del Slc11a1^s/Slc11a1^s
Genetic Background	B6.129S2-Casp1^tm1Flv

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1^tm1Flv mutation (2 available); any Casp1 mutation (42 available)
Casp4^del mutation (5 available); any Casp4 mutation (33 available)
Slc11a1^s mutation (0 available); any Slc11a1 mutation (40 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:124378 )

• when infected with 10⁵ Salmonella typhimurium, mice exhibit increased mortality compared to wild-type mice

immune system

cecum inflammation ( J:124378 )

• the ceca of mice infected with Salmonella typhimurium and treated with streptomycin exhibit increased inflammation with more edema, more neutrophil infiltration and epithelial disruption

increased susceptibility to bacterial infection ( J:124378 )

• when infected with 10⁵ Salmonella typhimurium, mice exhibit increased mortality compared to wild-type mice

• when infected with 10⁶ Salmonella typhimurium, spleen and mesenteric lymph nodes bacterial loads are increased to a greater extent than in either single allele homozygote

• following infection with Salmonella typhimurium, Peyer patches exhibit slightly increased bacterial load compared to in Slc11a1^s homozygotes

digestive/alimentary system

cecum inflammation ( J:124378 )

• the ceca of mice infected with Salmonella typhimurium and treated with streptomycin exhibit increased inflammation with more edema, more neutrophil infiltration and epithelial disruption

Allelic Composition	Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del
Genetic Background	B6.129S2-Casp1^tm1Flv

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♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

renal/urinary system

renal tubular necrosis ( J:97733 )

• reduced compared to controls after LPS induced acute kidney failure but not significantly

decreased renal glomerular filtration rate ( J:97733 )

• reduced after LPS induced acute kidney failure but less than in controls

kidney failure ( J:97733 )

• LPS induced acute kidney failure is also less severe

digestive/alimentary system

abnormal gut flora balance ( J:173245 )

• mice and co-housed wild-type mice exhibit expanded bacterial phylotypes compared with wild-type mice

increased susceptibility to induced colitis ( J:173245 )

• mice exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis compared with similarly treated wild-type mice

• mice transmit increased susceptibility to DSS-induced colitis to co-housed wild-type mice

immune system

increased susceptibility to induced colitis ( J:173245 )

• mice exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis compared with similarly treated wild-type mice

• mice transmit increased susceptibility to DSS-induced colitis to co-housed wild-type mice

decreased interleukin-1 beta secretion ( J:160545 )

• in LPS-primed bone marrow derived macrophages stimulated by S. typhimurium

Allelic Composition	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del Slc11a1^s/Slc11a1^s
Genetic Background	B6.129S2-Casp1^tm1Sesh Casp4^del

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1^tm1Sesh mutation (5 available); any Casp1 mutation (42 available)
Casp4^del mutation (5 available); any Casp4 mutation (33 available)
Slc11a1^s 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

Allelic Composition	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del
Genetic Background	B6.129S2(NOD)-Casp1^tm1Sesh Casp4^del

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♀	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

Allelic Composition	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del
Genetic Background	C3.129S2-Casp1^tm1Sesh Casp4^del

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♀	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

Allelic Composition	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del
Genetic Background	C3N.129S2-Casp1^tm1Sesh Casp4^del

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♀	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

Allelic Composition	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del
Genetic Background	involves: 129 * 129S2/SvPas * C57BL/6

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♀	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

Allelic Composition	Casp1^tm1Sesh/Casp1⁺ Casp4^del/Casp4⁺
Genetic Background	involves: 129S1/SvImJ * 129S2/SvPas * NOD

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♀	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 )

Allelic Composition	Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del Slc11a1^r/Slc11a1^r
Genetic Background	involves: 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1^tm1Flv mutation (2 available); any Casp1 mutation (42 available)
Casp4^del mutation (5 available); any Casp4 mutation (33 available)
Slc11a1^r mutation (2 available); any Slc11a1 mutation (40 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:124378 )

• when infected with 10⁶ Salmonella typhimurium, mice have a shorter time to death than Slc11a1^r homozygotes

immune system

increased susceptibility to bacterial infection ( J:124378 )

• when infected with 10⁶ Salmonella typhimurium, mice have a shorter time to death than Slc11a1 homozygotes

• when infected with 10⁶ Salmonella typhimurium, spleen and mesenteric lymph nodes bacterial loads are increased relative to in Slc11a1 homozygotes

• following infection with Salmonella typhimurium, Peyer patches exhibit slightly increased bacterial load compared to in Slc11a1^r homozygotes

Allelic Composition	Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del
Genetic Background	involves: 129S2/SvPas

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♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

decreased susceptibility to induced morbidity/mortality ( J:59893 )

• only 3 of 16 mice injected with B16M cells die after 12 days compared to all similarly treated wild-type mice

neoplasm

decreased metastatic potential ( J:59893 )

• mice injected with B16 cells exhibit reduced metastasis (by volume and density) in the liver compared with similarly treated wild-type mice

• mice injected with B16 cells exhibit decreased metastasis volume, an indicator of metastatic growth, compared with similarly treated wild-type mice

decreased tumor growth/size ( J:59893 )

• mice injected with B16 cells exhibit decreased metastasis volume, an indicator of metastatic growth, compared with similarly treated wild-type mice

Allelic Composition	Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del Il1r1^tm1Imx/Il1r1^tm1Imx
Genetic Background	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1^tm1Flv mutation (2 available); any Casp1 mutation (42 available)
Casp4^del mutation (5 available); any Casp4 mutation (33 available)
Il1r1^tm1Imx mutation (4 available); any Il1r1 mutation (39 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

immune system

decreased susceptibility to endotoxin shock ( J:43088 )

• resistance to endotoxin shock induced by high dose lipopolysaccharide (LPS)

♀	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 )

• 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

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 )

• also, mutant neurons are highly resistant to Ripk2-mediated cell death; transfecting caspase-1 into mutant neurons restores sensitivity to Ripk2-induced apoptosis

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 )

• 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

Allelic Composition	Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

immune system

decreased thymocyte apoptosis ( J:24258 )

• Fas mediated apoptosis in thymocytes is suppressed

impaired neutrophil chemotaxis ( J:124226 )

• following stimulation with monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD), neutrophil recruitment is impaired

decreased circulating interferon-gamma level ( J:115310 )

• serum levels are reduced in mice given Il12 daily

abnormal cytokine secretion ( J:24258 )

decreased interferon-gamma secretion ( J:115310 )

• significantly reduced levels of Ifn gamma are induced by Il12 in splenocytes

decreased interleukin-1 alpha secretion ( J:24258 )

• no Il1 alpha is released by monocytes in response to LPS

decreased interleukin-1 beta secretion ( J:24258 )

• no Il1 beta is released by monocytes in response to LPS

decreased interleukin-18 secretion ( J:115310 )

• significantly lower levels of Il18 are released by cultured splenocytes

• Il12 treatment fails to cause increased Il18 release but liver and spleen levels increase comparable to controls

decreased interleukin-6 secretion ( J:24258 )

• secretion by monocytes in response to LPS is reduced

decreased tumor necrosis factor secretion ( J:24258 )

• secretion by monocytes in response to LPS is reduced

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:57101 )

decreased susceptibility to endotoxin shock ( J:43088 )

• 10 fold increase in survival (from 6% in wild-type to 60%) of mice challenged with a high dose of LPS

increased susceptibility to bacterial infection ( J:117251 )

• macrophages infected with Legionella and cultured for 72 hours show a 200-fold increase in bacterial number

renal/urinary system

renal tubular necrosis ( J:69421 )

• reduced after ischemic reperfusion as compared to controls

kidney failure ( J:69421 )

• ischemic acute renal failure is less severe than in controls

homeostasis/metabolism

decreased circulating interferon-gamma level ( J:115310 )

• serum levels are reduced in mice given Il12 daily

hematopoietic system

decreased thymocyte apoptosis ( J:24258 )

• Fas mediated apoptosis in thymocytes is suppressed

impaired neutrophil chemotaxis ( J:124226 )

• following stimulation with monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD), neutrophil recruitment is impaired

cellular

decreased thymocyte apoptosis ( J:24258 )

• Fas mediated apoptosis in thymocytes is suppressed

impaired neutrophil chemotaxis ( J:124226 )

• following stimulation with monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD), neutrophil recruitment is impaired

endocrine/exocrine glands

decreased thymocyte apoptosis ( J:24258 )

• Fas mediated apoptosis in thymocytes is suppressed

Allelic Composition	Casp1^tm1Sesh/Casp1⁺ Casp4^del/Casp4⁺
Genetic Background	involves: 129S2/SvPas * C57BL/6

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♀	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

Allelic Composition	Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del
Genetic Background	involves: 129S2/SvPas * C57BL/6J

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♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

neoplasm

decreased incidence of tumors by chemical induction ( J:191239 )

• mice treated with 7,12-Dimethylbenz(a)anthracene/12-O-Tetradecanoylphorbol-13-acetate (DMBA) exhibit later onset and a lower incidence of tumors compared with type mice

integument

integument phenotype ( J:191239 )

N	• untreated or TPA, TNF or EGF-treated keratinocytes exhibit normal proliferation

homeostasis/metabolism

decreased incidence of tumors by chemical induction ( J:191239 )

• mice treated with 7,12-Dimethylbenz(a)anthracene/12-O-Tetradecanoylphorbol-13-acetate (DMBA) exhibit later onset and a lower incidence of tumors compared with type mice

Allelic Composition	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del Tg(Casp4)#Gne/0
Genetic Background	involves: 129S2/SvPas * C57BL/6 * NOD/ShiLtJ

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♀	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

Allelic Composition	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del Slc11a1^r/Slc11a1^s
Genetic Background	involves: 129/Sv * 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casp1^tm1Sesh mutation (5 available); any Casp1 mutation (42 available)
Casp4^del mutation (5 available); any Casp4 mutation (33 available)
Slc11a1^r mutation (2 available); any Slc11a1 mutation (40 available)
Slc11a1^s 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

Allelic Composition	Casp1^tm1Sesh/Casp1^tm1Sesh Casp4^del/Casp4^del
Genetic Background	NOD.129S2(B6)-Casp1^tm1Sesh Casp4^del/LtJ

Find Mice

♀	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 )

• 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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