Phenotypes Associated with This Genotype

Genotype
MGI:3804036

• Allelic Composition: Chuk^tm1Mpa/Chuk^tm1Mpa; Ikbkb^tm2Cgn/Ikbkb^tm2Cgn; Tg(Alb1-cre)7Gsc/0
• Genetic Background: involves: C57BL/6 * FVB/N

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

mortality/aging

decreased survivor rate ( J:137861 )

• most mice die by 7 months of age

premature death ( J:137861 )

• most mice die by 7 months of age

liver/biliary system

abnormal bile duct morphology ( J:137861 )

• the number of intact small portal bile ducts is reduced compared to in wild-type mice and exhibit signs of severe chronic cholestasis

• unobstructed bile ducts exhibit damaged, flattened epithelium surrounded by inflammatory foci with lymphocyte and ceroid macrophage infiltrate unlike in wild-type mice

• however, small bile duct development is normal at birth

• as the portal bile ducts are destroyed bile leaks between neighboring cells and the blood-bile barrier is disrupted

abnormal bile canaliculus morphology ( J:137861 )

• altered tubular arrangements of hepatocytes and severe dilations of the bile canaliculi are observed along with the disappearance of microvilli, formation of blebs and thickening of the pericanalicular ectoplasm

intrahepatic cholestasis ( J:137861 )

• severe chronic cholestasis in the liver

jaundice ( J:137861 )

homeostasis/metabolism

increased circulating bilirubin level ( J:137861 )

increased circulating alanine transaminase level ( J:137861 )

growth/size/body

cachexia ( J:137861 )

postnatal growth retardation ( J:137861 )

immune system

increased susceptibility to endotoxin shock ( J:137861 )

• following exposure to LPS, mice exhibit increased liver failure and hepatocyte apoptosis compared to similarly treated wild-type mice or single homozygous mice

endocrine/exocrine glands

abnormal bile duct morphology ( J:137861 )

• the number of intact small portal bile ducts is reduced compared to in wild-type mice and exhibit signs of severe chronic cholestasis

• unobstructed bile ducts exhibit damaged, flattened epithelium surrounded by inflammatory foci with lymphocyte and ceroid macrophage infiltrate unlike in wild-type mice

• however, small bile duct development is normal at birth

• as the portal bile ducts are destroyed bile leaks between neighboring cells and the blood-bile barrier is disrupted