Phenotypes Associated with This Genotype

Genotype
MGI:3776781

• Allelic Composition: Del(MTmt-Tk-mt-Nd5)1Jiha
• Genetic Background: involves: C57BL/6J * CBA

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

mortality/aging

premature death ( J:103743 )

• at day 218 to 277, all non-transplanted mice with less than 70% mutant mtDNA in their tails but greater than 88% in kidney cells die unlike mice from nuclear transplants with less than 5% mutant mtDNA that live longer than 300 days

cellular

teratozoospermia ( J:115155 )

♂

abnormal sperm midpiece morphology ( J:115155 )

♂ • middle piece abnormalities, including unevenly sterile and bending forms, are most often observed in mice with greater than 70% mutant mtDNA

abnormal sperm nucleus morphology ( J:115155 )

♂ • sperm nucleus abnormalities (pyknosis) are most often observed in mice with greater than 70% mutant mtDNA

absent sperm head ( J:115155 )

♂ • headless sperm are most often observed in mice with greater than 70% mutant mtDNA

decreased germ cell number ( J:115155 )

• spermatocytes and spermatids are reduced in mice with 69% to 80% and difficult to detect in mice with greater than 81% mutant mtDNA

oligozoospermia ( J:115155 )

♂ • male mice with greater than 69% mutant mtDNA exhibit reduced sperm cell numbers due to apoptosis of meiotically arrested cells

abnormal mitochondrial crista morphology ( J:72614 )

• cytochrome c oxidase-deficient cardiac mitochondria possess only tubular and bubble-like cristae

dilated mitochondrion ( J:72614 )

• cytochrome c oxidase-deficient cardiac mitochondria possess a swollen structure

arrest of male meiosis ( J:115155 )

♂ • in male mice with greater than 75% mutant mtDNA, spermatocytes arrest at the zygotene stage because of abnormal synapsis

asthenozoospermia ( J:115155 )

♂ • sperm from mice with 69% to 73% mutant mtDNA exhibit reduced sperm motility while it is absent in mice with more than 73% mutant mtDNA

abnormal mitochondrial ATP synthesis coupled electron transport ( J:72614 , J:92536 , J:103743 , J:115155 , J:132407 )

• cytochrome c oxidase activity is reduced compared to in wild-type mice in cardiac muscle in which the mutant mtDNA is present in 91.6% of total mitochondria (J:72614)

• cytochrome c oxidase activity is reduced compared to in wild-type mice in islet cells in which the mutant mtDNA is present in greater than 75% of total mitochondria (J:92536)

• cytochrome c oxidase activity is reduced in kidney and heart cells in non-transplanted mice in which the mutant mtDNA is present in 85% of total mitochondria but not in mice from nuclear transplants with less than 5% mutant mtDNA (J:103743)

• in mice with greater than 70% mutant mtDNA (J:115155)

• cytochrome c oxidase activity is reduced in the sperm of mice with greater than 73% mutant mtDNA (J:115155)

• however, mice with less than 68% mutant mtDNA are normal (J:115155)

• cytochrome c oxidase activity is reduced kidney cells of mice with 80% mutant mtDNA (J:132407)

reproductive system

teratozoospermia ( J:115155 )

♂

abnormal sperm midpiece morphology ( J:115155 )

♂ • middle piece abnormalities, including unevenly sterile and bending forms, are most often observed in mice with greater than 70% mutant mtDNA

abnormal sperm nucleus morphology ( J:115155 )

♂ • sperm nucleus abnormalities (pyknosis) are most often observed in mice with greater than 70% mutant mtDNA

absent sperm head ( J:115155 )

♂ • headless sperm are most often observed in mice with greater than 70% mutant mtDNA

decreased germ cell number ( J:115155 )

• spermatocytes and spermatids are reduced in mice with 69% to 80% and difficult to detect in mice with greater than 81% mutant mtDNA

oligozoospermia ( J:115155 )

♂ • male mice with greater than 69% mutant mtDNA exhibit reduced sperm cell numbers due to apoptosis of meiotically arrested cells

arrest of male meiosis ( J:115155 )

♂ • in male mice with greater than 75% mutant mtDNA, spermatocytes arrest at the zygotene stage because of abnormal synapsis

asthenozoospermia ( J:115155 )

♂ • sperm from mice with 69% to 73% mutant mtDNA exhibit reduced sperm motility while it is absent in mice with more than 73% mutant mtDNA

decreased litter size ( J:115155 )

• in mice with 69% to 73% mutant mtDNA

male infertility ( J:115155 )

♂ • male mice with greater than 73% mutant mtDNA are infertile

renal/urinary system

enlarged kidney ( J:103743 , J:132407 )

• in non-transplanted mice with 78% mutant mtDNA but not mice from nuclear transplants with less than 5% mutant mtDNA (J:103743)

• in mice with 80% mutant mtDNA (J:132407)

glomerulosclerosis ( J:132407 )

• in mice with 80% mutant mtDNA

dilated renal tubule ( J:132407 )

• in mice with 80% mutant mtDNA

dilated distal convoluted tubule ( J:103743 )

• cortical proximal and distal tubules are dilated in non-transplanted mice with 85% mutant mtDNA in kidney cells unlike in mice from nuclear transplants with less than 5% mutant mtDNA

dilated proximal convoluted tubule ( J:103743 )

• cortical proximal and distal tubules are dilated in non-transplanted mice with 85% mutant mtDNA in kidney cells unlike in mice from nuclear transplants with less than 5% mutant mtDNA

pale kidney ( J:132407 )

• in mice with 80% mutant mtDNA

kidney failure ( J:115155 )

• in mice with greater than 81% mutant mtDNA

homeostasis/metabolism

increased insulin secretion ( J:92536 )

• in mice in which the mutant mtDNA is present in 81-90% of total mitochondria

increased blood urea nitrogen level ( J:103743 )

• in non-transplanted mice with 78% mutant mtDNA but mice from nuclear transplants with less than 5% mutant mtDNA

decreased circulating glucose level ( J:92536 )

• in mice in which the mutant mtDNA is present in 81-90% of total mitochondria

increased circulating insulin level ( J:92536 )

• in mice in which the mutant mtDNA is present in 81-90% of total mitochondria

increased circulating lactate level ( J:103743 )

• blood lactate levels are high in non-transplanted mice with 78% mutant mtDNA unlike in mice from nuclear transplants with less than 5% mutant mtDNA

lactic acidosis ( J:115155 )

• mice with greater than 70% mutant mtDNA exhibit lactic acidosis

hearing/vestibular/ear

impaired hearing ( J:92536 )

• the severity hearing loss corresponds to a high percentage of mutant mitochondrial DNA

deafness ( J:115155 )

• in mice with greater than 81% mutant mtDNA

growth/size/body

decreased body weight ( J:103743 , J:115155 )

• non-transplanted mice with 78% mutant mtDNA exhibit a lower weight at day 150 than mice from nuclear transplants with less than 5% mutant mtDNA (J:103743)

• in mice with greater than 81% mutant mtDNA (J:115155)

abnormal postnatal growth ( J:103743 )

• non-transplanted mice with 78% mutant mtDNA grow slower than mice from nuclear transplants with less than 5% mutant mtDNA

enlarged kidney ( J:103743 , J:132407 )

• in non-transplanted mice with 78% mutant mtDNA but not mice from nuclear transplants with less than 5% mutant mtDNA (J:103743)

• in mice with 80% mutant mtDNA (J:132407)

behavior/neurological

reduced male mating frequency ( J:115155 )

♂ • copulation behavior is not observed in male mice with greater than 81% mutant mtDNA

cardiovascular system

heart block ( J:115155 )

• mice with greater than 81% mutant mtDNA exhibit heart block

muscle

myopathy ( J:115155 )

• in mice with greater than 81% mutant mtDNA

endocrine/exocrine glands

increased pancreatic alpha cell number ( J:92536 )

• the number of alpha cells is increased in mice in which the mutant mtDNA is present in 90% of total mitochondria

increased pancreatic beta cell number ( J:92536 )

• in mice in which the mutant mtDNA is present in 90% of total mitochondria

pancreatic islet hyperplasia ( J:92536 )

• in mice in which the mutant mtDNA is present in 90% of total mitochondria

increased insulin secretion ( J:92536 )

• in mice in which the mutant mtDNA is present in 81-90% of total mitochondria

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mitochondrial myopathy		DOID:699	OMIM:251900	J:103743