growth/size/body
• liver is larger in 10 week old mice and further enlarged at 40 weeks
|
• liver weight per body weight ratio is increased 2-fold at 10 weeks and 3-fold at 40 weeks
|
liver/biliary system
• mild sinusoidal fibrogenic changes and accumulations of lobular inflammatory cells are seen by 40 weeks of age
|
• increase in hepatocyte proliferation at 10 weeks of age
• however, no differences in hepatocyte apoptosis are seen at 10 or 40 weeks of age
|
• liver is larger in 10 week old mice and further enlarged at 40 weeks
|
• liver weight per body weight ratio is increased 2-fold at 10 weeks and 3-fold at 40 weeks
|
• triglyceride levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age
• however, no differences in liver levels of free fatty acids, free cholesterol, or phospholipids are seen
|
• hepatocytes acquire expression of an adipocyte-specific marker
|
• Mallory bodies are frequently seen in hepatocytes by 40 weeks of age
|
• absolute numbers of total liver cells are almost normal at 10 weeks of age but increased by 1.5-fold at 40 weeks
|
• cytoplasm of liver cells is weakly eosinophilic and contains numerous microvesicular vacuoles containing lipids at 10 weeks of age; vacuolar changes are seen mainly around the central vein
• steatotic changes are more prominent in male than female mice
• by 40 weeks of age, livers show fatty changes of increased severity throughout the hepatic lobule such that aged liver resembles adipocytes in fat tissues
• however, no fibrotic changes are seen in the liver
|
pale liver
(
J:90905
)
• livers are light-colored at 10 weeks of age and homogenously white in color at 40 weeks
|
• hepatocellular carcinomas are seen in 5 of 6 males and 3 of 6 females; the hepatocellular carcinomas develop within liver adenomas and contain many fewer cytoplasmic lipid droplets than the adenomas
|
• macroscopic hepatic tumors are present in 66% of male and 30% of female mice at 40-44 weeks of age; nodular lesions resemble liver adenomas and cells with large droplets in the cytoplasm are prominent in most adenomas
|
homeostasis/metabolism
• cholesterol ester levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age
|
• glucose levels are lower in fasted mutants both before and after oral glucose administration
|
• serum insulin levels are reduced at 12 weeks of age
|
• serum levels are elevated at 40 weeks of age but not at 10 weeks of age
|
• serum levels are elevated at 40 weeks of age but not at 10 weeks of age
|
• serum levels are elevated at 40 weeks of age but not at 10 weeks of age
|
• intraperitoneal insulin injection reduces glucose levels by a greater amount than in wild-type mice indicating insulin hypersensitivity
|
• 16-carbon monosaturated fatty acids (C16:1) and C18:1 fatty acids are increased in livers of 10 week old mice and C16:0, C16:1, C18:0, C18:1, and C18:2 fatty acids are increased in livers of 40 week old mice
|
• triglyceride levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age
• however, no differences in liver levels of free fatty acids, free cholesterol, or phospholipids are seen
|
neoplasm
• hepatocellular carcinomas are seen in 5 of 6 males and 3 of 6 females; the hepatocellular carcinomas develop within liver adenomas and contain many fewer cytoplasmic lipid droplets than the adenomas
|
• macroscopic hepatic tumors are present in 66% of male and 30% of female mice at 40-44 weeks of age; nodular lesions resemble liver adenomas and cells with large droplets in the cytoplasm are prominent in most adenomas
|
• 2 mutants with hepatocellular carcinoma show lung metastasis
|
cardiovascular system
• mild sinusoidal fibrogenic changes and accumulations of lobular inflammatory cells are seen by 40 weeks of age
|
cellular
• however, no differences in hepatocyte apoptosis are seen at 10 or 40 weeks of age
• increase in hepatocyte proliferation at 10 weeks of age
|
• cholesterol ester levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age
|
• hepatic hydrogen peroxide levels in the liver are increased 7-fold, indicating increased production of reactive oxygen species
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
hepatocellular carcinoma | DOID:684 |
OMIM:114550 |
J:90905 | |
steatotic liver disease | DOID:9452 |
OMIM:228100 |
J:90905 |