Phenotypes Associated with This Genotype

Genotype
MGI:5444474

• Allelic Composition: Cox10^tm1Ctm/Cox10^tm1Ctm; Tg(Camk2a-cre)#Szi/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * C57BL/6J * CBA

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

mortality/aging

premature death ( J:188773 )

• die between 8 and 12 months of age

growth/size/body

decreased body weight ( J:188773 )

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

behavior/neurological

impaired coordination ( J:188773 )

• decrease in rotarod performance first seen at 3 and 4 months of age for males and females, respectively

abnormal locomotor activation ( J:188773 )

• 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

cellular

abnormal mitochondrial physiology ( J:188773 )

• 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

decreased brain weight ( J:188773 )

• brain weight is normal at 1-4 months of age, however by 8 months of age, brains weigh about half of control weight

abnormal cerebral cortex morphology ( J:188773 )

• severe cortical atrophy by 8 months of age

abnormal cingulate gyrus morphology ( J:188773 )

• neuronal cell death in the cingulate cortex at 4 months of age, but not earlier

abnormal piriform cortex morphology ( J:188773 )

• mutants show oxidative damage in the piriform cortex at 4 months of age and neuronal cell death at this time but not earlier

neurodegeneration ( J:188773 )

• 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

neuron degeneration ( J:188773 )

• mutants consistently show neuronal cell death in the cingulate cortex, piriform cortex, and hippocampus/dentate gyrus at 4 months of age, but not earlier

hippocampal neuron degeneration ( J:188773 )

• the hippocampus/dentate gyrus and CA1 region shows neuronal loss at 4 months of age

abnormal nervous system physiology ( J:188773 )

• mutants show metabolic changes in the brain, with elevated levels of lactate and a decrease in n-acetyl aspartate

abnormal glial cell physiology ( J:188773 )

• 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

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:188773 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cytochrome-c oxidase deficiency disease		DOID:3762	OMIM:PS220110	J:188773