Mouse Genome Informatics
hm
    Opa3m1Votr/Opa3m1Votr
involves: C3H * C57BL/6JCrl
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• most mice die within 12 to 16 weeks
• healthy mice deteriorate rapidly and often die within 7 days
• some mice die prior to weaning, with possible gestational loss

vision/eye
• optic nerves exhibit increased axon degeneration, opaque mitochondria and mitochondrial activity compared to in wild-type mice
• severely reduced

cardiovascular system
• left and right ventricle myocardium exhibits matrix expansion, interstitial fibrosis, cardiac muscle fiber deposits, atrophy and hyperatrophy of residual muscle fibers, and vacuolation of muscle fibers unlike in wild-type mice
• thinned left ventricle wall

behavior/neurological
• in compromised mice
• in compromised mice
• in compromised mice
• splayed gait

nervous system
• optic nerves exhibit increased axon degeneration, opaque mitochondria and mitochondrial activity compared to in wild-type mice
• in the spinal cord, brain and optic nerve

growth/size
• in compromised mice
• snubbed snout
• weigh less than wild-type starting at P5 and are only 40% of that in wild-type at P30 (J:188346)
• 22% reduction in body and tibial lengths

adipose tissue
• in compromised mice
• brown adipose tissue (BAT) exhibits an increase in total lipid area and lipid droplet size, indicating entrapment of lipid in BAT
• 2.5-fold increase in interscapular BAT weight, with parallel increases in total lipid area and lipid droplet size, indicating that BAT is engorged with lipid
• 71% reduction in adipocyte size
• intra-abdominal white adipose tissue (WAT) shows clear areas of 'browning', with a sift from large unilocular to small multilocular lipid droplets and areas of more intense mitochondrial staining
• reduction in proportionate intra-abdominal (epididymal and retroperitoneal) WAT weight

cellular
• optic nerves exhibit an increase in the number of opaque mitochondria compared to in wild-type mice
• optic nerves exhibit increased mitochondrial activity compared to in wild-type mice (J:181670)
• mitochondrial function is impaired in adipose tissue resulting in a 16-fold elevation in circulating 3-methylglutaconic acid (J:188346)

craniofacial
• snubbed snout

homeostasis/metabolism
• 16-fold elevation in circulating 3-methylglutaconic acid
• surface body temperature is about 5 degrees C lower than in wild-type
• despite normal drinking
• content of mitochondrial-specific lipid, cardiolipin, and its metabolic precursor, phosphatidylglycerol, is increased by 49 and 92% respectively, in the liver
• increase in hepatic triglycerol content
• however circulating triglycerol is normal

liver/biliary system
• livers are glycogen depleted compared to in wild-type mice
• increase in hepatic triglycerol content
• however circulating triglycerol is normal
• liver weight is increased by 30%
• livers show evidence of hepatic steatosis, characterized by large lipid rafts

muscle

skeleton
• while there is no significant change in germinal width of the growth plate, the number of cells in this zone is increased by 28%
• the hypertrophic zone is normal
• width of the proliferative zone is reduced by 19% but shows no alteration in the number of cells in this zone

Mouse Models of Human Disease
OMIM IDRef(s)
3-methylglutaconic Aciduria, Type III; MGCA3 258501 J:181670 , J:188346