Phenotypes associated with this allele

• Allele Symbol: Casp8^tm1Clie
• Allele Name: targeted mutation 1, Christian Liedtke
• Allele ID: MGI:4461018
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Casp8^tm1Clie/Casp8^tm1Clie Tg(Alb1-cre)7Gsc/0	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:5618132
cn2	Casp8^tm1Clie/Casp8^tm1Clie Ikbkg^tm1.1Chtr/Ikbkg^tm1.1Chtr Tg(Alb1-cre)7Gsc/0	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:5618136
cn3	Casp8^tm1Clie/Casp8^tm1Clie Map3k7^tm1Aki/Map3k7^tm1Aki Tg(Alb1-cre)7Gsc/0	involves: 129P2/OlaHsd * FVB/N	MGI:4461038

Genotype
MGI:5618132

cn1

• Allelic Composition: Casp8^tm1Clie/Casp8^tm1Clie; Tg(Alb1-cre)7Gsc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

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

homeostasis/metabolism

abnormal circulating enzyme level ( J:218665 )

♂ • mice exhibit an increase in serum transaminases levels

decreased susceptibility to injury ( J:218665 )

♂ • mice are protected from induction of apoptosis and liver injury by Fas or lipopolysaccarides and exhibit 100% survival compared to 90% mortality within 24 horus of liver injury in controls

increased susceptibility to injury ( J:218665 )

♂ • mice exhibit increased necrotic damage, reduced survival, increased aspartate aminotransferase and alanine aminotransferase levels, and increased infiltration of CD11b+F4/80+ macrophages in response to acute liver injury induced by concanavalin A

immune system

liver inflammation ( J:218665 )

♂ • livers show small inflammatory infiltrates of granulocytes and monocytes and increased serum transaminases, indicating basal liver inflammation

liver/biliary system

liver inflammation ( J:218665 )

♂ • livers show small inflammatory infiltrates of granulocytes and monocytes and increased serum transaminases, indicating basal liver inflammation

Genotype
MGI:5618136

cn2

• Allelic Composition: Casp8^tm1Clie/Casp8^tm1Clie; Ikbkg^tm1.1Chtr/Ikbkg^tm1.1Chtr; Tg(Alb1-cre)7Gsc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

liver/biliary system

abnormal biliary tract morphology ( J:218665 )

♂ • mice exhibit biliary lesions

abnormal liver morphology ( J:218665 )

♂ • mice exhibit necrotic liver injury (three types of injury are seen) which is maximal at 6-8 weeks of age

♂ • 34% of mice exhibit few white liver lesions identified as necrotic areas (type I liver)

♂ • 40% of mice exhibit multilocular, visible white liver lesions with features of parenchymal necroses or bile infarcts and increased liver weight (type II liver)

♂ • 26% of mice exhibit yellow livers, increased liver size, multilocular yellow lesions resulting in massive necrotic destruction of the liver associated with multiple bile infarcts, and exhibit dwarfism (type III liver)

♂ • increase in cell proliferation (not hepatocytes) in the liver

enlarged liver ( J:218665 )

♂ • hepatomegaly is seen in mice with type II and III livers

hepatic necrosis ( J:218665 )

♂ • mice exhibit necrotic liver injury which is maximal at 6-8 weeks of age

♂ • ageing mice recover from necrotic liver injury and are protected from steatosis but develop liver fibrosis

liver fibrosis ( J:218665 )

♂ • ageing mice recover from necrotic liver injury but develop liver fibrosis

intrahepatic cholestasis ( J:218665 )

♂

growth/size/body

decreased body size ( J:218665 )

♂ • dwarfism is seen in mice with type III livers

enlarged liver ( J:218665 )

♂ • hepatomegaly is seen in mice with type II and III livers

homeostasis/metabolism

increased circulating bilirubin level ( J:218665 )

♂ • increase in bilirubin levels in mice with type III livers

abnormal circulating enzyme level ( J:218665 )

♂ • serum transaminase levels are increased in mice with type II and III livers

increased circulating alkaline phosphatase level ( J:218665 )

♂ • alkaline phosphatase levels are elevated in correlation to severity of liver injury

increased bile salt level ( J:218665 )

♂ • increase in bile acid levels in mice with type III livers

neoplasm

neoplasm ( J:218665 )

♂N • mice do not develop hepatocellular carcinoma are remain tumor free up to 60 weeks of age

Genotype
MGI:4461038

cn3

• Allelic Composition: Casp8^tm1Clie/Casp8^tm1Clie; Map3k7^tm1Aki/Map3k7^tm1Aki; Tg(Alb1-cre)7Gsc/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

mortality/aging ( J:160521 )

N • mice exhibit normal survival throughout 40 weeks

liver/biliary system

abnormal bile duct morphology ( J:160521 )

• mice exhibit strong dysplasia, absence of small bile ducts, and increased bile duct proliferation compared with wild-type mice

bile duct proliferation ( J:160521 )

abnormal liver morphology ( J:160521 )

• mice exhibit hyperproliferation, dysplasia, and reduction of biliary epithelial cells unlike wild-type mice

focal hepatic necrosis ( J:160521 )

• at an earlier age and to a larger extent than in Map3k7^tm1Aki/ Map3k7^tm1Aki Tg(Alb1-cre)7Gsc mice

homeostasis/metabolism

increased circulating bilirubin level ( J:160521 )

• serum bilirubin levels are increased compared to in wild-type mice and Map3k7^tm1Aki/ Map3k7^tm1Aki Tg(Alb1-cre)7Gsc mice

increased circulating alanine transaminase level ( J:160521 )

• milder than in Map3k7^tm1Aki/ Map3k7^tm1Aki Tg(Alb1-cre)7Gsc mice

increased circulating aspartate transaminase level ( J:160521 )

growth/size/body

postnatal growth retardation ( J:160521 )

endocrine/exocrine glands

abnormal bile duct morphology ( J:160521 )

• mice exhibit strong dysplasia, absence of small bile ducts, and increased bile duct proliferation compared with wild-type mice

bile duct proliferation ( J:160521 )