Phenotypes Associated with This Genotype

Genotype
MGI:5519060

• Allelic Composition: Gclc^tm1Tdal/Gclc^tm1Tdal; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

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

mortality/aging

premature death ( J:202376 )

• mice become moribund at 30 days of age and are euthanized

growth/size/body

postnatal growth retardation ( J:202376 )

• although normal at birth, mice become growth retarded after 14 days of age

homeostasis/metabolism

abnormal homeostasis ( J:202376 )

• glutathione levels in the liver are about 37% of normal at 14 days of age

• glutathione levels in plasma are extremely low at 14 days of age

increased circulating alanine transaminase level ( J:202376 )

• plasma levels are dramatically elevated by 28 days of age

increased circulating aspartate transaminase level ( J:202376 )

• plasma levels are dramatically elevated by 28 days of age

liver/biliary system

abnormal liver morphology ( J:202376 )

• vacuolated hepatocytes are diffusely present at 21 days of age

• both macrovesicular and microvesicular vacuoles are found

• vacuoles contain neutral lipid

• scattered instances of single cell death

• increased number of binucleate hepatocytes

hepatic steatosis ( J:202376 )

• increasing steatosis from 21 days (26%) to 28 days of age (69%)

cellular

abnormal endoplasmic reticulum morphology ( J:202376 )

• loss of lamellar rough endoplasmic reticulum in hepatocytes by 28 days of age

• replaced by small vesicles lacking ribosomes

abnormal mitochondrial morphology ( J:202376 )

• 20% of mitochondria are morphologically abnormal in hepatocytes at 21 days of age

decreased mitochondrial number ( J:202376 )

• mitochondrion number in hepatocytes is 42% of control numbers at 14 days and 16% at 28 days of age

abnormal mitochondrial physiology ( J:202376 )

• mitochondrial respiratory control ratios in hepatocytes are reduced at 21 days

• decreased oxygen consumption at state 3 respiration

• poorly coupled at 25 and 28 days

• decreased membrane potentials

• reduced liver ATP

• increased lipid peroxidation