Phenotypes Associated with This Genotype

Genotype
MGI:3793729

• Allelic Composition: Atp7a^Mo-vbr/Y
• Genetic Background: Not Specified

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

mortality/aging

premature death ( J:38977 )

♂ • some hemizygous males live several months before dying

postnatal lethality ( J:38977 )

♂ • death of hemizygous males can occur within several days of birth

cellular

abnormal mitochondrial physiology ( J:44695 )

♂ • the decrease in succinate-cytochrome c reductase activity in muscle indicates that complex II is defective and mitochondrial function is probably disrupted

♂ • skeletal muscle has a reduced PCr recovery rate indicating mitochondrial dysfunction

♂ • however, total ATP content is normal in muscle and brain

cardiovascular system

abnormal aorta morphology ( J:5397 )

♂

abnormal aorta elastic fiber morphology ( J:5397 )

♂ • lysine content of aortic elastin is higher than controls indicating less conversion to Lys-derived aldehydes and therefore less cross-links

♂ • aortic tissue has diminished cross-link content

increased aortic weight ( J:5397 )

♂ • without obvious aneurysm, aorta dry weight is significantly greater than control; in aneurismal aortas, dry weight is >3-fold greater than controls

aortic aneurysm ( J:5397 )

♂ • in areas of aneurysm, tissue is largely made up of collagen, whereas normal tissue is mainly collagen and elastin

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:5397 )

♂N • serum copper levels are not significantly different from controls

decreased creatine level ( J:44695 )

♂ • 19% reduction in total creatine in skeletal muscle

♂ • however, total creatine level in brain is normal

abnormal pH regulation ( J:44695 )

♂ • intracellular pH is higher in the brain

abnormal enzyme/coenzyme activity ( J:44695 , J:53559 )

♂ • succinate cytochrome c reductase activity is reduced by about 55% in skeletal muscle (J:44695)

♂ • cytochrome oxidase, creatine kinase, and hexokinase maximal activities are decreased in the brain (J:44695)

♂ • lactate dehydrogenase activity is increased in the brain (J:44695)

♂ • however, no differences are seen in maximal cytochrome oxidase, citrate synthase, or lactate dehydrogenase activity in muscle (J:44695)

♂ • mice exhibit an approximate 2-fold decrease in cytochrome c oxidase and a 1.4-fold decrease in NADH:cytochrome c reductase activities (J:53559)

♂ • the electron transfer activity of cytochrome c oxidase is affected and heme aa3 content is reduced by a factor of about 2 (J:53559)

♂ • however, no changes in the overall rates of mitochondrial oxidative phosphorylation are seen and overall mitochondrial oxygen consumption capacities in the brain cortex are normal (J:53559)

decreased creatine kinase activity ( J:44695 )

♂ • creatine kinase activity is decreased in the brain

reproductive system

male infertility ( J:13473 )

♂ • Background Sensitivity: on some backgrounds males are viable but sterile

pigmentation

abnormal coat/hair pigmentation ( J:13473 )

♂ • this genotype is near white with dark extremities, a himalayan-like pattern

integument

abnormal coat/hair pigmentation ( J:13473 )

♂ • this genotype is near white with dark extremities, a himalayan-like pattern

abnormal cutaneous collagen fibril morphology ( J:5397 )

♂ • collagen has much lower proportion of cross-linked components than controls

abnormal skin condition ( J:5397 )

♂ • extensibility of skin is significantly greater than Atp7a^Mo-blo males or control Atp7a^Mo-br females

decreased skin tensile strength ( J:5397 )

♂ • breaking force of skin is significantly lower than Atp7a^Mo-blo males or control Atp7a^Mo-br females

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Menkes disease		DOID:1838	OMIM:309400	J:53559
NOT	mitochondrial encephalomyopathy	DOID:890		J:44695