Phenotypes associated with this allele

• Allele Symbol: Casp8^tm1.1Raz
• Allele Name: targeted mutation 1.1, Razqallah Hakem
• Allele ID: MGI:5546196
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Casp8^tm1.1Raz/Casp8^tm1.1Raz	involves: 129P2/OlaHsd	MGI:5546197
cx2	Casp8^tm1.1Raz/Casp8^tm1.1Raz Ripk3^tm1Vmd/Ripk3^tm1Vmd	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:5546328
cx3	Casp8^tm1.1Raz/Casp8^tm1.1Raz Ripk3^tm1Vmd/Ripk3^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:5546345
cx4	Casp8^tm1.1Raz/Casp8^tm1.1Raz Otulin^em1Gvl/Otulin^em1Gvl Ripk3^tm1Vmd/Ripk3^tm1Vmd	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:7256604

Genotype
MGI:5546197

cn1

• Allelic Composition: Casp8^tm1.1Raz/Casp8^tm1.1Raz
• Genetic Background: involves: 129P2/OlaHsd

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

mortality/aging

embryonic lethality, complete penetrance ( J:82759 , J:170815 )

• homozygous mice do not survive past E12.5 (J:82759)

• by E11.5 (J:170815)

cardiovascular system

abnormal vitelline vasculature morphology ( J:170815 )

• disrupted vascular pattern at E10.5

abnormal blood circulation ( J:170815 )

• hyperemia in the abdominal region

embryo

abnormal vitelline vasculature morphology ( J:170815 )

• disrupted vascular pattern at E10.5

wavy neural tube ( J:170815 )

• undulation of the neural tube

nervous system

wavy neural tube ( J:170815 )

• undulation of the neural tube

Genotype
MGI:5546328

cx2

• Allelic Composition: Casp8^tm1.1Raz/Casp8^tm1.1Raz; Ripk3^tm1Vmd/Ripk3^tm1Vmd
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

mortality/aging

mortality/aging ( J:170814 , J:170815 )

N • born at expected Mendelian ratio (J:170814)

N • viable (J:170815)

growth/size/body

growth/size/body region phenotype ( J:170814 )

N • indistinguishable body mass compared to control animals (heterozygous for the Casp8 allele and homozygous for the Ripk3) between days 20 to 160

enlarged spleen ( J:170814 , J:170815 )

• at 15 weeks of age (J:170814)

• from 2 to 8 months (J:170815)

• high levels of CD3+ T cells and CD19+ B cells contribute to greater number of leukocytes in spleen (J:170815)

cellular

decreased thymocyte apoptosis ( J:170814 )

• resistant to CD95-activated apoptosis in thymocytes

decreased macrophage apoptosis ( J:170815 )

• resistant to Fas-activated cell death

decreased hepatocyte apoptosis ( J:170814 )

• comparing to control animals upon stimulation by pro-hepatocyte apoptosis agent (anti-CD95 antibody)

liver/biliary system

abnormal liver physiology ( J:170815 )

• resistant to TNF-dependent fatal liver hepatitis pathway

decreased hepatocyte apoptosis ( J:170814 )

• comparing to control animals upon stimulation by pro-hepatocyte apoptosis agent (anti-CD95 antibody)

immune system

immune system phenotype ( J:170815 )

N • no evidence of skin inflammation at up to 6 months of age

decreased thymocyte apoptosis ( J:170814 )

• resistant to CD95-activated apoptosis in thymocytes

enlarged thymus ( J:170814 )

• at 15 weeks of age

enlarged spleen ( J:170814 , J:170815 )

• at 15 weeks of age (J:170814)

• from 2 to 8 months (J:170815)

• high levels of CD3+ T cells and CD19+ B cells contribute to greater number of leukocytes in spleen (J:170815)

increased leukocyte cell number ( J:170815 )

• significantly greater numbers of leukocytes in secondary lymphoid tissues

increased B cell number ( J:170815 )

• increase in the number of CD19+ B cells in secondary lymphoid tissues

increased T cell number ( J:170814 , J:170815 )

• normal mature T-lymphocyte subsets in 1 month old mice, but show a marked increased in B220+, CD3+ cells with age (J:170814)

• contributes to lymphadenopathy and splenomegaly (J:170815)

• abnormal T cell accumulation following Fas death-receptor-induced death pathways activation due to the failure to response to both apoptosis and necroptosis (J:170815)

• increase in the number of CD3+ T cells in secondary lymphoid tissues is the primary cause of increase the increase in the number leukocytes in these tissues (J:170815)

increased spleen white pulp amount ( J:170815 )

abnormal macrophage physiology ( J:170815 )

• bone marrow derived macrophages are resistant to RIP3 dependent necroptosis

decreased macrophage apoptosis ( J:170815 )

• resistant to Fas-activated cell death

enlarged lymph nodes ( J:170814 )

• at 15 weeks of age

lymph node hyperplasia ( J:170815 )

• lymphadenopathy with more lymphoid cells in splenic white pulp

• enlarged cervical lymph node at 6 months and axial lymph node at 2 to 8 months of age

enlarged axillary lymph nodes ( J:170815 )

• enlarged axial lymph node at 2 to 8 months of age

enlarged cervical lymph nodes ( J:170815 )

• enlarged cervical lymph node at 6 months

large lymphoid organs ( J:170814 )

• normal lymphoid organs comparing to control animals at 4 weeks but display progressive severe lymphoaccumulation at 15 weeks

increased inflammatory response ( J:170815 )

• lymphocytic infiltrates in the salivary glands, pancreas and lamina propria of both the stomach and small intestine

hematopoietic system

hematopoietic system phenotype ( J:170814 , J:170815 )

N • T-lymphocyte proliferation and activation in response to immune challenge is comparable to control animals (J:170814)

N • CD11b+F4/80+ bone marrow-derived mononuclear production is not affected (J:170815)

N • myeloid and lymphocyte cell generation in bone marrow, spleen, thymus, and lymph node of DKO mice is unaffected compared to littermate controls (J:170815)

N • no defect in T-cell activation in response to antigen (J:170815)

decreased thymocyte apoptosis ( J:170814 )

• resistant to CD95-activated apoptosis in thymocytes

enlarged thymus ( J:170814 )

• at 15 weeks of age

enlarged spleen ( J:170814 , J:170815 )

• at 15 weeks of age (J:170814)

• from 2 to 8 months (J:170815)

• high levels of CD3+ T cells and CD19+ B cells contribute to greater number of leukocytes in spleen (J:170815)

increased leukocyte cell number ( J:170815 )

• significantly greater numbers of leukocytes in secondary lymphoid tissues

increased B cell number ( J:170815 )

• increase in the number of CD19+ B cells in secondary lymphoid tissues

increased T cell number ( J:170814 , J:170815 )

• normal mature T-lymphocyte subsets in 1 month old mice, but show a marked increased in B220+, CD3+ cells with age (J:170814)

• contributes to lymphadenopathy and splenomegaly (J:170815)

• abnormal T cell accumulation following Fas death-receptor-induced death pathways activation due to the failure to response to both apoptosis and necroptosis (J:170815)

• increase in the number of CD3+ T cells in secondary lymphoid tissues is the primary cause of increase the increase in the number leukocytes in these tissues (J:170815)

increased spleen white pulp amount ( J:170815 )

abnormal macrophage physiology ( J:170815 )

• bone marrow derived macrophages are resistant to RIP3 dependent necroptosis

decreased macrophage apoptosis ( J:170815 )

• resistant to Fas-activated cell death

endocrine/exocrine glands

decreased thymocyte apoptosis ( J:170814 )

• resistant to CD95-activated apoptosis in thymocytes

enlarged thymus ( J:170814 )

• at 15 weeks of age

Genotype
MGI:5546345

cx3

• Allelic Composition: Casp8^tm1.1Raz/Casp8^tm1.1Raz; Ripk3^tm1Vmd/Ripk3⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

mortality/aging

embryonic lethality, complete penetrance ( J:170815 )

• by about E11.5

cardiovascular system

abnormal vitelline vasculature morphology ( J:170815 )

• at E10.5, disrupted yolk sac vascular pattern

embryo

abnormal vitelline vasculature morphology ( J:170815 )

• at E10.5, disrupted yolk sac vascular pattern

embryonic growth arrest ( J:170815 )

• arrest at about E11.0

abnormal visceral yolk sac blood island morphology ( J:170815 )

• fragmented at E10.5

Genotype
MGI:7256604

cx4

• Allelic Composition: Casp8^tm1.1Raz/Casp8^tm1.1Raz; Otulin^em1Gvl/Otulin^em1Gvl; Ripk3^tm1Vmd/Ripk3^tm1Vmd
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J

embryo

embryo phenotype ( J:312394 )

N • mice born at normal Mendelian ratios

immune system

immune system phenotype ( J:312394 )

N • no skin inflammation

enlarged lymph nodes ( J:312394 )

• lymphoproliferative syndrome by age 4 months

integument

integument phenotype ( J:312394 )

N • no dermatitis and normal epidermal thickness