Mouse Genome Informatics
hm1
    Mpv17/Mpv17
involves: CFW
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• death between 2 and 9 months of age (J:10661)
• homozygotes are fertile and live long enough to reproduce (J:27358)
• survival to 52 weeks of age has been reported (J:62419)
• median life span is 645 days unlike in wild-type mice that survive longer (J:143355)

growth/size/body
• after 1 year of age
• weight loss associated with death

behavior/neurological
• become inactive prior to death

homeostasis/metabolism
N
• unlike human patients with the hepatocerebral form of mitochondrial DNA depletion syndrome, mice fail to exhibit hypoglycemia or abnormal glucose tolerance (J:143355)
• at 6-8 weeks of age
• beginning at 5 months, lactate levels are moderately higher than in wild-type mice
• beginning at 5 months, serum creatine kinase levels are higher than in wild-type mice
• at 6-8 weeks of age (J:10661)
• at 6-8 weeks of age (J:10661)
• at 18 months without changes in the creatinine and urea serum levels (J:143355)
• evident at 8 weeks of age (J:62419)
• 95% of proteinuria due to albuminuria (J:108252)
• at 2 years of age

hematopoietic system
• reduced RBC count at 6-8 weeks of age
• reduced hemoglobin levels at 6-8 weeks of age
• severe normocytic and normochromic anemia seen between 2 and 6 months of age

renal/urinary system
• at 2 years of age
• early fusion of foot processes in glomerular visceral epithelial cells
• eventual diffuse fusion of foot processes and vacuolation of cell cytoplasm
• almost complete flattening of the foot processes at 180 days
• 2-fold increase in reactive oxygen species (J:108252)
• 2.5-fold increase in lipid peroxidation adducts (J:108252)
• the amount of mitochondrial DNA in glomeruli at 6 months and 2 years is decreased compared to in wild-type mice (J:143355)
• segmental mesangial sclerosis at 50 days of age
• glomeruli become enlarged and capillaries collapse (J:10661)
• glomeruli become occluded with hyaline material (J:10661)
• enlargement slight at 50 days of age (J:108252)
• glomeruli eventually become totally obliterated by hyaline masses (J:10661)
• at 18 months, mice exhibit focal segmental glomerulosclerosis that by 2 years of age develops into frank degenerative changes of the glomeruli unlike in wild-type mice (J:143355)
• glomeruli become enlarged (J:10661)
• enlargement slight at 50 days of age (J:108252)
• increased kidney weight at 52 weeks of age
• hyaline and scarred segmental lesions at 180 days
• microcystic dilation of renal tubules
• at 2 years of age, degenerative changes in the glomeruli are accompanied by degenerative abnormalities in the tubular system, with dilation and formation of pseudocysts, parenchymal loss, and interstitial fibrosis unlike in wild-type mice
• at 2 years, kidney mitochondrial DNA content is reduced 47% compared to in wild-type mice
• at 6-8 weeks of age (J:10661)
• at 18 months without changes in the creatinine and urea serum levels (J:143355)
• evident at 8 weeks of age (J:62419)
• 95% of proteinuria due to albuminuria (J:108252)
• increased urinary volume

cardiovascular system
• beginning at 5 months, sinusoidal spaces collapse unlike in wild-type mice
• significant hypertension

hearing/vestibular/ear
• pronounced OHC loss at 2 months of age
• severe degeneration of the organ of Corti by 7 months (J:48662)
• severe degeneration of the spiral ligament by 7 months (J:48662)
• moderate degenerative alterations at 2 months of age (J:48662)
• severe degeneration of the stria vascularis by 7 months (J:48662)
• at 2 months of age, poor brainstem evoked responses are obtained at 1-32 kHz
• by 7 months of age, no brainstem evoked responses can be elicited
• severe sensorineural hearing loss as early as 2 months after birth (J:48661)

nervous system
• pronounced OHC loss at 2 months of age
• marked loss of spiral ganglion cells by 7 months
• loss of cochlear neurons

adipose tissue

cellular
N
• despite defects in mitochondria morphology, mice exhibit normal mitochondrial response to hypothermia (J:143355)
• the mitochondrial DNA content in the liver and muscle is very low compared to in wild-type mice
• proliferating and non-proliferating mouse embryonic fibroblast exhibit a decrease in mitochondrial DNA over time compared to an increase in wild-type cells
• the amount of mitochondrial DNA in glomeruli at 6 months and 2 years is decreased compared to in wild-type mice
• at 2 years, kidney mitochondrial DNA content is reduced 47% compared to in wild-type mice
• however, mitochondrial DNA content in the brain is normal
• older mice exhibit disappearance of internal cristae unlike in wild-type mice
• older mice exhibit mitochondrial ballooning unlike in wild-type mice

endocrine/exocrine glands
• at 2 years, sebaceous gland and annexa size and numbers are decreased compared to in wild-type mice
• at 2 years

liver/biliary system
N
• despite abnormal liver morphology, mice do not exhibit increased susceptibility to chemically-induced liver damage using valporic acid (J:143355)
• beginning at 5 months, scattered degeneration of discrete areas of hepatic lobules occurs unlike in wild-type mice
• beginning at 5 months, sinusoidal spaces collapse unlike in wild-type mice
• beginning at 5 months, hepatocytes are swollen with shrunken nuclei unlike wild-type cells
• beginning at 5 months, inflammatory infiltrate concentrates on the portal triads unlike in wild-type mice

pigmentation
• mice develop gray coat color 5 to 6 months after birth unlike wild-type mice

integument
• at 2 years, sebaceous gland and annexa size and numbers are decreased compared to in wild-type mice
• at 2 years
• mice develop gray coat color 5 to 6 months after birth unlike wild-type mice
• at 2 years, hair follicles are hypotrophic compared to in wild-type mice
• at 2 years of age, mice exhibit disorganization of the muscle layer
• at 2 years, mice exhibit severe atrophy of the skin layers, with thinning of the epidermis unlike in wild-type mice
• at 2 years
• late-onset

muscle
• at 2 years of age, mice exhibit disorganization of the muscle layer

skeleton
• severe degeneration of the spiral ligament by 7 months (J:48662)