Phenotypes associated with this allele

• Allele Symbol: Ripk3^tm1Vmd
• Allele Name: targeted mutation 1, Vishva M Dixit
• Allele ID: MGI:3028853
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ripk3^tm1Vmd/Ripk3^tm1Vmd	B6.129-Ripk3^tm1Vmd	MGI:5308652
hm2	Ripk3^tm1Vmd/Ripk3^tm1Vmd	involves: 129S1/Sv * 129X1/SvJ	MGI:5538615
hm3	Ripk3^tm1Vmd/Ripk3^tm1Vmd	involves: 129S1/Sv * 129X1/SvJ * C57BL/6N	MGI:3028861
cn4	Fadd^tm1Mpa/Fadd^tm1Mpa Ripk3^tm1Vmd/Ripk3^tm1Vmd Tg(Vil1-cre)997Gum/0	B6.Cg-Fadd^tm1Mpa Ripk3^tm1Vmd Tg(Vil1-cre)997Gum	MGI:5293399
cx5	Ppm1b^Gt(AW0406)Wtsi/Ppm1b^Gt(AW0406)Wtsi Ripk3^tm1Vmd/Ripk3^tm1Vmd	B6.129-Ripk3^tm1Vmd Ppm1b^Gt(AW0406)Wtsi	MGI:6111453
cx6	Casp8^tm1.1Raz/Casp8^tm1.1Raz Ripk3^tm1Vmd/Ripk3^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:5546345
cx7	Casp8^tm1.1Raz/Casp8^tm1.1Raz Ripk3^tm1Vmd/Ripk3^tm1Vmd	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:5546328
cx8	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
cx9	Birc2^tm1.1Rbr/Birc2^tm1.1Rbr Birc3^tm1.1Rbr/Birc3^tm1.1Rbr Ripk3^tm1Vmd/Ripk3^tm1Vmd	involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6 * SJL	MGI:5319384
cx10	Birc2^tm1.1Rbr/Birc2^tm1.1Rbr Birc3^tm1.1Rbr/Birc3^tm1.1Rbr Ripk3^tm1Vmd/Ripk3^+	involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6 * SJL	MGI:5319381

Genotype
MGI:5308652

hm1

• Allelic Composition: Ripk3^tm1Vmd/Ripk3^tm1Vmd
• Genetic Background: B6.129-Ripk3^tm1Vmd

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

mortality/aging

decreased susceptibility to induced morbidity/mortality ( J:179279 )

• do not develop severe hypothermia or die after treatment with TNF unlike wild-type mice

immune system

decreased inflammatory response ( J:179279 )

• do not develop severe hypothermia or die after treatment with TNF unlike wild-type mice

• however, intestinal damage 3 and 6 hours after TNF treatment is similar to wild-type mice

• onset of mortality following cecal ligation and puncture is delayed and fewer mice die compared to wild-type mice

Genotype
MGI:5538615

hm2

• Allelic Composition: Ripk3^tm1Vmd/Ripk3^tm1Vmd
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

mortality/aging ( J:204622 )

N • unlike previously reported in J:179279, mice exhibit normal mortality in response to polymicrobial septic shock following cecal ligation and perforation

Genotype
MGI:3028861

hm3

• Allelic Composition: Ripk3^tm1Vmd/Ripk3^tm1Vmd
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6N

immune system

immune system phenotype ( J:87683 )

N • at 6 to 14 weeks of age, homozygotes are healthy and fertile and display a normal immune system phenotype, including:

N • normal macrophage, lymphocyte, and natural killer cell development

N • normal NF-kappaB signaling in response to human TNF, cross-linking of the B- or T-cell antigen receptors, peptidoglycan, and LPS

N • normal thymocyte apoptosis in response to different stimuli, with no differences in sensitivity to the phorbol ester phorbol myristate acetate, the calcium ionophore ionomycin, or the glucocorticoid dexamethasone, or Fas ligand

N • normal lymphocyte proliferation in response to various mitogens in vitro

N • normal DNP-specific IgG1production after immunization with the T-dependent antigen DNP-OVA

N • normal IL-1beta, IL-6, and TNF production after LPS treatment

Genotype
MGI:5293399

cn4

• Allelic Composition: Fadd^tm1Mpa/Fadd^tm1Mpa; Ripk3^tm1Vmd/Ripk3^tm1Vmd; Tg(Vil1-cre)997Gum/0
• Genetic Background: B6.Cg-Fadd^tm1Mpa Ripk3^tm1Vmd Tg(Vil1-cre)997Gum

mortality/aging

mortality/aging ( J:175865 )

N • mice exhibit normal survival

digestive/alimentary system

digestive/alimentary phenotype ( J:175865 )

N • mice exhibit normal small intestine and colon morphology

Genotype
MGI:6111453

cx5

• Allelic Composition: Ppm1b^{Gt(AW0406)Wtsi}/Ppm1b^{Gt(AW0406)Wtsi}; Ripk3^tm1Vmd/Ripk3^tm1Vmd
• Genetic Background: B6.129-Ripk3^tm1Vmd Ppm1b^{Gt(AW0406)Wtsi}

cellular

cellular phenotype ( J:243815 )

N • normal resistance to necroptosis in caecum after intravenous injection with mouse Tnf

Genotype
MGI:5546345

cx6

• 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:5546328

cx7

• 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:7256604

cx8

• 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

Genotype
MGI:5319384

cx9

• Allelic Composition: Birc2^tm1.1Rbr/Birc2^tm1.1Rbr; Birc3^tm1.1Rbr/Birc3^tm1.1Rbr; Ripk3^tm1Vmd/Ripk3^tm1Vmd
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6 * SJL

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:182515 )

• mice survive to E15.5

Genotype
MGI:5319381

cx10

• Allelic Composition: Birc2^tm1.1Rbr/Birc2^tm1.1Rbr; Birc3^tm1.1Rbr/Birc3^tm1.1Rbr; Ripk3^tm1Vmd/Ripk3⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6 * SJL

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:182515 )

• mice survive to E12.5