growth/size/body
weight loss
(
J:172422
)
• aged mutants become leaner by 10.7% for males and 14.9% for females, with a significant decrease of their body weights at 1 year of age
|
• lobular architecture of the liver is distorted by the development of hyperplastic hepatocyte plates
|
homeostasis/metabolism
• serum levels of alanine aminotransferase are higher than in controls
|
• serum levels of aspartate aminotransferase are higher than in controls
|
• injection of a single dose of diethylnitrosamine (DEN) on P15 results in an increase in the number and size of (hepatocellular carcinoma) liver tumors in mutants compared to controls
|
immune system
• intraperitoneal LPS injection elicits a stronger liver damage response in mutants than in controls as indicated by higher serum alanine aminotransferase levels
• mutants show a 130% increase in spleen size 14 days after LPS challenge as compared to 98% increase in controls indicating increased systemic inflammatory response
• mutants show increased inflammatory cell infiltration into hepatic parenchyma after LPS challenge
• circulating IL-6 and TNFalpha levels are increased following LPS injection
• LPS stimulation of isolated hepatocytes results in increased IL-6 secretion by mutant hepatocytes compared to controls
|
• 93% of mutant livers contain areas with infiltrate of inflammatory cells, concentrating around the portal triads with extension into the parenchyma
• necrotic zones of livers are always associated with inflammatory cells, whereas inflammation is occasionally observed without necrosis
• 8 of 19 aged mutants develop focal microgranuloma consisting of mononuclear inflammatory cells
|
liver/biliary system
• 93% of mutant livers contain areas with infiltrate of inflammatory cells, concentrating around the portal triads with extension into the parenchyma
• necrotic zones of livers are always associated with inflammatory cells, whereas inflammation is occasionally observed without necrosis
• 8 of 19 aged mutants develop focal microgranuloma consisting of mononuclear inflammatory cells
|
• one or several foci of pallor are noticeable on the liver surface of 34% of analyzed mutants
• beginning at 5 months of age, regenerative foci are noticeable in the liver and nodular regenerative hyperplasia is seen from 8 months of age
• hepatic inflammation and necrosis, leading to nodular regenerative hyperplasia
|
• lobular architecture of the liver is distorted by the development of hyperplastic hepatocyte plates
|
• hepatic parenchyma shows regenerative hyperplasia, with 13 of 19 livers having nodule formation
• the space between hepatocytes is reduced inside the nodules
|
• massive hepatocyte degeneration is seen inside of or surrounding the hyperplastic nodules, in association with vacuoles containing eosinophilic material, but not in the liver parenchyma
|
• liver shows small focal areas as well as large areas of parenchymal necrosis, with necrosis observed in 47% of mutants
|
• liver shows small focal areas of parenchymal necrosis
|
• from 12-18 months of age, one or a few hepatocellular adenomas are frequently seen in mutants; tumors bulge from the liver surface, are often paler than the hepatic parenchyma, but sometimes darker or red when accompanied by bleeding
• tumors are unencapsulated, well delimited and show expanding masses of hepatocytes
|
• fibrosis is seen at the portal triads but not near the necrosis or into the parenchyma
|
neoplasm
• injection of a single dose of diethylnitrosamine (DEN) on P15 results in an increase in the number and size of (hepatocellular carcinoma) liver tumors in mutants compared to controls
|
• from 12-18 months of age, one or a few hepatocellular adenomas are frequently seen in mutants; tumors bulge from the liver surface, are often paler than the hepatic parenchyma, but sometimes darker or red when accompanied by bleeding
• tumors are unencapsulated, well delimited and show expanding masses of hepatocytes
|
cellular
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
hepatocellular adenoma | DOID:0050868 | J:172422 |