Mouse Genome Informatics

involves: 129X1/SvJ * C57BL/6 * C57BL/6J * CBA
phenotype observed in females
phenotype observed in males
N normal phenotype
• die between 8 and 12 months of age

• mutants weight less than littermate controls after 4 and 5 months of age, for females and males, respectively

• decrease in rotarod performance first seen at 3 and 4 months of age for males and females, respectively
• at 3 months of age, mutants start to decrease their nocturnal activity and by 4 months, cycles of hyperactivity are seen and continue throughout their life span

• mutants exhibit 80% of mitochondrial respiratory complex IV (CIV) activity of control levels in the cortex at 1 month of age and 33% of control levels by 4 months of age
• mutants exhibit decreased CIV activity in the hippocampus as well

nervous system
• brain weight is normal at 1-4 months of age, however by 8 months of age, brains weigh about half of control weight
• severe cortical atrophy by 8 months of age
• neuronal cell death in the cingulate cortex at 4 months of age, but not earlier
• mutants show oxidative damage in the piriform cortex at 4 months of age and neuronal cell death at this time but not earlier
• mutants exhibit progressive encephalopathy, with small lesions in the piriform cortex at 4 months of age, lesions in the striatum, outer cortical layers and hippocampus by 6 months of age, and massive degeneration of the cortex by 8 months of age
• mutants consistently show neuronal cell death in the cingulate cortex, piriform cortex, and hippocampus/dentate gyrus at 4 months of age, but not earlier
• the hippocampus/dentate gyrus and CA1 region shows neuronal loss at 4 months of age
• mutants show metabolic changes in the brain, with elevated levels of lactate and a decrease in n-acetyl aspartate
• mutants exhibit a dramatic increase in GFAP immunoreactivity in the cortex and somewhat smaller increase in the hippocampus and piriform cortex at 4-5 months of age, indicating reactive glia

• mutants exhibit decreased mitochondrial respiratory complex IV enzymatic activity in the cortex and hippocampus

Mouse Models of Human Disease
Mitochondrial Complex IV Deficiency 220110 J:188773