Phenotypes Associated with This Genotype

Genotype
MGI:3700375

• Allelic Composition: Ikbkg^tm1.1Mpa/Ikbkg^tm1.1Mpa; Tg(Alb1-cre)7Gsc/0
• Genetic Background: involves: C57BL/6 * FVB/N

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

liver/biliary system

liver inflammation ( J:118336 )

♀ • 8 week old mice show signs of steatohepatitis in the liver, characterized by immune cell infiltration into the parenchyma

♀ • in 8-week old mice, hepatocytes show features of large-cell dysplasia with strong anisokaryosis; large areas of irregularly shaped glycogen deposits are detected

abnormal liver morphology ( J:118336 )

♀ • at 6 months, livers show macroscopic nodules

♀ • focal areas of lipid accumulation and low-grade dysplastic nodules with expansive growth are observed

abnormal hepatocyte morphology ( J:118336 )

♀ • at 6 months, hepatocytes show lipid deposition and ballooning

♀ • in 8-week old mice, hepatocytes show features of large-cell dysplasia with strong anisokaryosis; large areas of irregularly shaped glycogen deposits are detected

abnormal hepatocyte mitochondrial morphology ( J:118336 )

♀ • mitochondria of hepatocytes appear swollen and display a reduction in mitochondrial crests compared to wild-type at 8 weeks of age

hepatic steatosis ( J:118336 )

♀ • at 6 months, mice show signs of steatosis and increased lipid deposition in hepatocytes

increased hepatocellular carcinoma incidence ( J:118336 )

♀ • multiple tumors are found in livers of 12-month old males; malignant liver tumors are present in all mice examined

♀ • average number of tumors per mouse is 5.75 with average size of 8.58 mm

♀ • tumors show expansive growth, increased cellularity, broad trabecular growth pattern in 4 to 6 layers, eosinophilia, higher cytoplasmic index compared to non malignant areas, and complete absence of portal tracts

♀ • tumors show increased proliferation and higher mitotic indices (~1.44 per high-power field)

♀ • tumors at 9 months show dysplastic foci and nodules

neoplasm

increased hepatocellular carcinoma incidence ( J:118336 )

♀ • multiple tumors are found in livers of 12-month old males; malignant liver tumors are present in all mice examined

♀ • average number of tumors per mouse is 5.75 with average size of 8.58 mm

♀ • tumors show expansive growth, increased cellularity, broad trabecular growth pattern in 4 to 6 layers, eosinophilia, higher cytoplasmic index compared to non malignant areas, and complete absence of portal tracts

♀ • tumors show increased proliferation and higher mitotic indices (~1.44 per high-power field)

♀ • tumors at 9 months show dysplastic foci and nodules

immune system

abnormal cytokine secretion ( J:118336 )

♀ • cytokine expression is upregulated in mutants

abnormal inflammatory response ( J:118336 )

♀ • upon LPS injection, NF kappa b activation is completely absent

increased susceptibility to endotoxin shock ( J:137861 )

♀ • following exposure to LPS, mice exhibit increased liver failure and hepatocyte apoptosis compared to similarly treated wild-type mice

liver inflammation ( J:118336 )

♀ • 8 week old mice show signs of steatohepatitis in the liver, characterized by immune cell infiltration into the parenchyma

♀ • in 8-week old mice, hepatocytes show features of large-cell dysplasia with strong anisokaryosis; large areas of irregularly shaped glycogen deposits are detected

cellular

abnormal hepatocyte mitochondrial morphology ( J:118336 )

♀ • mitochondria of hepatocytes appear swollen and display a reduction in mitochondrial crests compared to wild-type at 8 weeks of age

increased apoptosis ( J:118336 )

♀ • 8-week old mice show an increase in apoptotic cells in the liver

increased cell proliferation ( J:118336 )

♀ • livers show increased proliferation

♀ • at 8 weeks, there is a significant increase in progenitor cells and activation of oval cells in the liver

homeostasis/metabolism

decreased circulating glucose level ( J:118336 )

♀ • mice show a decrease in spontaneous serum glucose levels compared to controls

increased circulating alanine transaminase level ( J:118336 )

♀ • mice show elevated serum levels of alanine aminotransferase (ALT) at 3 weeks, indicative of hepatocyte damage; ALT levels are further increased at 8 weeks

abnormal enzyme/coenzyme activity ( J:118336 )

♀ • mice show increased JNK kinase activity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
steatotic liver disease		DOID:9452	OMIM:228100	J:118336