Phenotypes for Tg(Mup3-Plau)350-2Eps MGI:5781017 MGI Mouse

abnormal endoplasmic reticulum morphology ( J:233146 )

• high fat diet fed mice show distended and dilated endoplasmic reticulum

increased hepatocyte apoptosis ( J:233146 )

• livers of high fat diet fed mice exhibit continuous hepatocyte death and compensatory proliferation

• hepatocytes treated with PA show more extensive lipotoxic cell death than wild-type hepatocytes

• PA treated hepatocytes treated with the chemical chaperons 4-phenylbutyrate (4-PBA) and tauro-ursodeoxycholic acid (TUDCA), which reduce ER stress, show a more pronounced attenuation of cell death than wild-type hepatocytes

hepatic necrosis ( J:233146 )

• livers of high fat diet fed mice show increased apoptotic and necrotic cell death

abnormal circulating alanine transaminase level ( J:233146 )

• mice fed a high fat diet starting at 6 weeks of age maintain high serum alanine aminotransferase (ALT) levels throughout the observation period

• high fat diet fed mice treated with TUDCA at 16 weeks of age exhibit reduced serum ALT levels

increased liver cholesterol level ( J:233146 )

• mice fed a high fat diet exhibit elevated liver cholesterol levels

• high fat diet fed mice treated with TUDCA at 16 weeks of age exhibit reduced hepatic cholesterol levels

increased liver free fatty acids level ( J:233146 )

• mice fed a standard chow diet show an increase in C16:0 palmitic acid and longer chain fatty acid in the liver compared to wild-type mice, which is further enhanced by high fat diet feeding

increased liver triglyceride level ( J:233146 )

• mice fed a high fat diet exhibit elevated liver triglycerides

• high fat diet fed mice treated with TUDCA at 16 weeks of age exhibit hepatic triglyceride levels

increased interleukin-1 beta secretion ( J:233146 )

• high fat diet fed mice show increased levels of IL-1beta in the liver at 24 weeks of age

increased tumor necrosis factor secretion ( J:233146 )

• high fat diet fed mice show increased levels of TNF in the liver at 24 weeks of age

• TUDCA treatment of high fat diet fed mice inhibits the TNF increase seen in the liver

liver inflammation ( J:233146 )

• mice fed a high fat diet exhibit extensive immune infiltration into the liver and numerous ballooning hepatocytes, indicating non-alcoholic steatohepatitis

• mice fed a high fat diet show an increase in the number of F4/80-positive macrophages in the liver

• TUDCA treatment of high fat diet fed mice inhibits the increase in macrophage infiltration in the liver

increased hepatocyte apoptosis ( J:233146 )

• livers of high fat diet fed mice exhibit continuous hepatocyte death and compensatory proliferation

• hepatocytes treated with PA show more extensive lipotoxic cell death than wild-type hepatocytes

• PA treated hepatocytes treated with the chemical chaperons 4-phenylbutyrate (4-PBA) and tauro-ursodeoxycholic acid (TUDCA), which reduce ER stress, show a more pronounced attenuation of cell death than wild-type hepatocytes

hepatic necrosis ( J:233146 )

• livers of high fat diet fed mice show increased apoptotic and necrotic cell death

liver hyperplasia ( J:233146 )

• 30% of normal chow fed mice display a few tiny nodules in the liver at 40 weeks of age, indicating hyperplasia

increased liver cholesterol level ( J:233146 )

• mice fed a high fat diet exhibit elevated liver cholesterol levels

• high fat diet fed mice treated with TUDCA at 16 weeks of age exhibit reduced hepatic cholesterol levels

increased liver free fatty acids level ( J:233146 )

• mice fed a standard chow diet show an increase in C16:0 palmitic acid and longer chain fatty acid in the liver compared to wild-type mice, which is further enhanced by high fat diet feeding

increased liver triglyceride level ( J:233146 )

• mice fed a high fat diet exhibit elevated liver triglycerides

• high fat diet fed mice treated with TUDCA at 16 weeks of age exhibit hepatic triglyceride levels

liver inflammation ( J:233146 )

• mice fed a high fat diet exhibit extensive immune infiltration into the liver and numerous ballooning hepatocytes, indicating non-alcoholic steatohepatitis

• mice fed a high fat diet show an increase in the number of F4/80-positive macrophages in the liver

• TUDCA treatment of high fat diet fed mice inhibits the increase in macrophage infiltration in the liver

abnormal hepatocyte morphology ( J:233146 )

• mice fed normal chow exhibit hepatocyte damage at 5 weeks of age but this disappears at 24 weeks, except for mild inflammation and spotty necrosis

• mice fed a high fat diet exhibit numerous ballooning hepatocytes

• high fat diet fed mice treated with TUDCA at 16 weeks of age exhibit attenuation of hepatocyte ballooning

hepatic steatosis ( J:233146 )

• mice fed a standard chow diet exhibit mild spontaneous lipid accumulation in the liver at 5 weeks of age that is diminished by 16 weeks of age

• mice fed a high fat diet show extensive lipid accumulation in the liver

• high fat diet fed mice treated with TUDCA at 16 weeks of age exhibit attenuation of hepatosteatosis

liver fibrosis ( J:233146 )

• mice fed a high fat diet show pericelluar and bridging fibrosis in the liver

increased liver tumor incidence ( J:233146 )

• high fat diet fed mice develop small tumors on the liver surface by 32 weeks of age and large tumors at 40 weeks

increased hepatocellular carcinoma incidence ( J:233146 )

• 30% of tumors larger than 2 mm are hepatocellular carcinomas, similar to human steatohepatitic hepatocellular carcinomas, although some show a classical thick trabecular pattern

• hepatocellular carcinoma progenitor cell-transplanted mutants develop multiple hepatocellular carcinoma nodules after 5 months

increased liver adenoma incidence ( J:233146 )

• 70% of tumors are either typical or steatohepatic adenomas