Phenotypes for Speer6-ps1 Tjp1 Tjp2 MGI:6719082 MGI Mouse

mortality/aging

premature death ( J:306936 )

• 70-80% die by 4 weeks and all die by 6 weeks of age

postnatal lethality, incomplete penetrance ( J:306936 )

• mice start to die around 2 weeks of age

growth/size/body

increased liver weight ( J:306936 )

• mean liver weight-to-body weight ratio is increased

liver/biliary system

abnormal hepatic duct morphology ( J:306936 )

• marker analysis shows no, or rare, bile ducts in the periportal zone of the liver

abnormal liver morphology ( J:306936 )

• liver is yellowish

• targeting of tight junctions and apical molecules is disrupted in the liver

• marker analysis indicates that liver zonation is perturbed

• however, no liver inflammation or fibrosis are seen

abnormal liver sinusoid morphology ( J:306936 )

• the lumina of the sinusoidal vessels are not clear

• marker analysis shows that sinusoidal vessels in the liver are injured

increased liver weight ( J:306936 )

• mean liver weight-to-body weight ratio is increased

abnormal hepatic cord morphology ( J:306936 )

• the hepatic cords are not well-organized in the liver

abnormal bile canaliculus morphology ( J:306936 )

• normal bile canaliculi are hardly seen

abnormal hepatocyte morphology ( J:306936 )

• individual hepatocytes appear slightly swollen with vacuole-like structures inside

• hepatocytes exhibit ectopic luminal structures around their basolateral domains

• hepatocyte cellular polarity is disrupted, with an unclear distinction between the apical and basolateral plasma membrane domains

small liver ( J:306936 )

abnormal liver physiology ( J:306936 )

• mice show disruption of the hepatic barrier

• bile transport into bile canaliculi is diminished

increased hepatocyte proliferation ( J:306936 )

• mice show an increase in Ki-67+ hepatocytes, indicating increased hepatocyte proliferation

homeostasis/metabolism

increased circulating bilirubin level ( J:306936 )

• mice show increased levels of total bilirubin and direct bilirubin

increased circulating LDL cholesterol level ( J:306936 )

increased circulating alanine transaminase level ( J:306936 )

increased circulating alkaline phosphatase level ( J:306936 )

• mice show increased levels of alkaline phosphatase

• however, gamma-glutamyl transferase levels are normal

increased circulating aspartate transaminase level ( J:306936 )

increased bile salt level ( J:306936 )

• mice show increased levels of bile acids

cardiovascular system