Phenotypes Associated with This Genotype

Genotype
MGI:3041261

• Allelic Composition: Met^tm1Sst/Met^tm1Sst; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

abnormal susceptibility to injury induced morbidity/mortality ( J:89236 )

• mutants are more vulnerable to hepatectomy surgery and most are either moribund or die by 48 hours after surgery

liver/biliary system

liver hemorrhage ( J:89236 )

• mutants develop hemorrhagic liver destruction within the first few hours in response to apoptotic stimuli induced by Fas (Tnfrsf6) antibody compared to only minor liver damage in controls

abnormal hepatocyte physiology ( J:89236 )

• primary hepatocytes show reduced phagocytic activity towards bacteria (E.coli) than control cells

increased hepatocyte apoptosis ( J:89236 )

• hepatocytes exhibit increased sensitivity to Fas (Tnfrsf6)-induced apoptosis

impaired liver regeneration ( J:89236 )

• the ability of mutant livers to clear necrotic tissue and to repopulate the injured (by CCl₄ exposure) area by regenerating hepatocytes is impaired

• associated with a persistent inflammatory reaction, overproduction of osteopontin, early and prominent dystrophic calcification, and impaired hepatocyte scattering/migration into diseased areas

liver failure ( J:89236 )

• 80% of mutants die of acute liver failure in response to apoptotic stimuli induced by Fas (Tnfrsf6) antibody while controls survive

cardiovascular system

liver hemorrhage ( J:89236 )

• mutants develop hemorrhagic liver destruction within the first few hours in response to apoptotic stimuli induced by Fas (Tnfrsf6) antibody compared to only minor liver damage in controls

homeostasis/metabolism

abnormal response to injury ( J:89236 )

• mutants exhibit delayed healing after toxic liver injury induced by CCl₄ exposure

abnormal susceptibility to injury induced morbidity/mortality ( J:89236 )

• mutants are more vulnerable to hepatectomy surgery and most are either moribund or die by 48 hours after surgery

impaired wound healing ( J:89236 )

• hepatocytes fail to migrate in a standard wound healing assay

cellular

increased hepatocyte apoptosis ( J:89236 )

• hepatocytes exhibit increased sensitivity to Fas (Tnfrsf6)-induced apoptosis