Phenotypes Associated with This Genotype

Genotype
MGI:5762654

cn2

• Allelic Composition: Gfer^tm1.1Crg/Gfer^tm1.1Crg; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129 * C57BL/6 * DBA

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

liver/biliary system

abnormal liver morphology ( J:227242 )

• progressively coarsened and granular by 8 weeks

• after 6 months, mice develop nodular foci of high-grade dysplasia in the liver

abnormal hepatocyte mitochondrial morphology ( J:227242 )

• swollen, abnormally shaped and with increased spacing or loss of cristae in hepatocyte mitochondria at 2 weeks of age; persistent to a lesser magnitude at 8 weeks

increased liver weight ( J:227242 )

• higher liver to body weight ratio at 4 to 6 weeks

decreased liver cholesterol level ( J:227242 )

• at 8 weeks of age

increased liver cholesterol level ( J:227242 )

• modestly at 2 weeks of age

• however, levels are normal at 4 weeks of age

increased liver triglyceride level ( J:227242 )

• at 2 and 4 weeks of age

• however, levels are normal at 8 weeks of age

hepatic necrosis ( J:227242 )

• at 8 weeks of age

focal hepatic necrosis ( J:227242 )

• focal hepatocyte necrosis at 4 weeks of age

hepatic steatosis ( J:227242 )

• macro- and micro vesicular steatosis with hepatocyte swelling and minimal inflammation at 2 weeks of age

• reduced at 4 weeks of age

macrovesicular hepatic steatosis ( J:227242 )

microvesicular hepatic steatosis ( J:227242 )

increased hepatocellular carcinoma incidence ( J:227242 )

• at 1 year, most mice develop hepatocellular carcinomas with tumor cells that are pleomorphic and often steatotic with frequent mitotic figures and variably anaplastic nuclei

liver fibrosis ( J:227242 )

• pericellular fibrosis at 2 weeks of age

• periportal fibrosis at 4 weeks of age

• bridging fibrosis at 8 weeks of age

pale liver ( J:227242 )

• milky white by 2 weeks of age

• however, livers regain normal color by 4 weeks

abnormal liver physiology ( J:227242 )

• prominent bile ductular proliferation at 4 weeks of age

• ductular proliferation at 8 weeks of age

• atypical ductular proliferation at 2 and 4 weeks of age

• cellular proliferation occurs in oval/biliary cells and parenchyma at 4 and 8 weeks of age

increased hepatocyte apoptosis ( J:227242 )

• at 2 weeks of age but decreasing progressively at 4 and 8 weeks of age

increased hepatocyte proliferation ( J:227242 )

• at 4 and 8 weeks

liver inflammation ( J:227242 )

• scattered lobular mixed inflammation with focal hepatocyte necrosis and prominent bile ductular proliferation at 4 weeks of age

• increasing portal/perioral and lobular mixed inflammation

abnormal oval cell physiology ( J:227242 )

• increased proliferation at 4 and 8 weeks of age

homeostasis/metabolism

increased circulating alanine transaminase level ( J:227242 )

• at 4 and 8 weeks of age

decreased liver cholesterol level ( J:227242 )

• at 8 weeks of age

increased liver cholesterol level ( J:227242 )

• modestly at 2 weeks of age

• however, levels are normal at 4 weeks of age

increased liver triglyceride level ( J:227242 )

• at 2 and 4 weeks of age

• however, levels are normal at 8 weeks of age

growth/size/body

decreased body weight ( J:227242 )

• at 4 and 6 weeks

• however, body weight is normal at 1, 2 and 8 weeks

increased liver weight ( J:227242 )

• higher liver to body weight ratio at 4 to 6 weeks

cellular

abnormal endoplasmic reticulum morphology ( J:227242 )

• dilated in hepatocytes with robust lipid deposition at 2 weeks of age; persistent to a lesser magnitude at 8 weeks

abnormal hepatocyte mitochondrial morphology ( J:227242 )

• swollen, abnormally shaped and with increased spacing or loss of cristae in hepatocyte mitochondria at 2 weeks of age; persistent to a lesser magnitude at 8 weeks

abnormal mitochondrial crista morphology ( J:227242 )

• increased spacing or loss of cristae in hepatocyte mitochondria at 2 weeks of age

abnormal mitochondrial shape ( J:227242 )

• in hepatocyte mitochondria at 2 weeks of age

decreased mitochondrial number ( J:227242 )

• in hepatocyte at 2 weeks of age

dilated mitochondrion ( J:227242 )

• in hepatocyte mitochondria at 2 weeks of age

increased hepatocyte apoptosis ( J:227242 )

• at 2 weeks of age but decreasing progressively at 4 and 8 weeks of age

increased hepatocyte proliferation ( J:227242 )

• at 4 and 8 weeks

abnormal cellular respiration ( J:227242 )

• in hepatocyte mitochondria at 2 weeks of age

• however, respiration activity has recovered by 4 and 8 weeks of age

neoplasm

increased hepatocellular carcinoma incidence ( J:227242 )

• at 1 year, most mice develop hepatocellular carcinomas with tumor cells that are pleomorphic and often steatotic with frequent mitotic figures and variably anaplastic nuclei

immune system

liver inflammation ( J:227242 )

• scattered lobular mixed inflammation with focal hepatocyte necrosis and prominent bile ductular proliferation at 4 weeks of age

• increasing portal/perioral and lobular mixed inflammation