Phenotypes Associated with This Genotype

Genotype
MGI:5312681

• Allelic Composition: Opa3^m1Votr/Opa3^m1Votr
• Genetic Background: involves: C3H * C57BL/6JCrl

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

mortality/aging

premature death ( J:181670 )

• most mice die within 12 to 16 weeks

• healthy mice deteriorate rapidly and often die within 7 days

preweaning lethality, incomplete penetrance ( J:181670 )

• some mice die prior to weaning, with possible gestational loss

vision/eye

abnormal optic nerve morphology ( J:181670 )

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

abnormal retina layer morphology ( J:181670 )

• thin

decreased retina ganglion cell number ( J:181670 )

• at 3 to 4 months

thin retina ganglion layer ( J:181670 )

thin retina inner plexiform layer ( J:181670 )

abnormal retina nerve fiber layer morphology ( J:181670 )

• thin

thin retina outer nuclear layer ( J:181670 )

abnormal vision ( J:181670 )

• severely reduced

cardiovascular system

abnormal ventricle myocardium morphology ( J:181670 )

• 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

thin interventricular septum ( J:181670 )

abnormal heart left ventricle morphology ( J:181670 )

• thinned left ventricle wall

dilated heart left ventricle ( J:181670 )

dilated heart right ventricle ( J:181670 )

cardiac interstitial fibrosis ( J:181670 )

dilated cardiomyopathy ( J:181670 )

behavior/neurological

abnormal pilomotor reflex ( J:181670 )

• in compromised mice

tremors ( J:181670 )

• in compromised mice

hunched posture ( J:181670 )

• in compromised mice

abnormal gait ( J:181670 )

• splayed gait

decreased locomotor activity ( J:181670 )

nervous system

decreased retina ganglion cell number ( J:181670 )

• at 3 to 4 months

abnormal optic nerve morphology ( J:181670 )

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

axon degeneration ( J:181670 )

• in the spinal cord, brain and optic nerve

growth/size/body

short snout ( J:181670 )

• snubbed snout

decreased birth body size ( J:181670 )

decreased body weight ( J:181670 , J:188346 )

• weigh less than wild-type starting at P5 and are only 40% of that in wild-type at P30 (J:188346)

decreased body length ( J:188346 )

• 22% reduction in body and tibial lengths

postnatal growth retardation ( J:181670 , J:188346 )

increased liver weight ( J:188346 )

• liver weight is increased by 30%

adipose tissue

decreased total body fat amount ( J:181670 )

• in compromised mice

abnormal brown adipose tissue morphology ( J:188346 )

• brown adipose tissue (BAT) exhibits an increase in total lipid area and lipid droplet size, indicating entrapment of lipid in BAT

increased brown adipose tissue amount ( J:188346 )

• 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

decreased fat cell size ( J:188346 )

• 71% reduction in adipocyte size

abnormal abdominal fat pad morphology ( J:181670 )

• absent

abnormal white adipose tissue morphology ( J:188346 )

• 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

decreased white adipose tissue amount ( J:188346 )

• reduction in proportionate intra-abdominal (epididymal and retroperitoneal) WAT weight

cellular

cardiac interstitial fibrosis ( J:181670 )

abnormal mitochondrial morphology ( J:181670 )

• optic nerves exhibit an increase in the number of opaque mitochondria compared to in wild-type mice

abnormal mitochondrial physiology ( J:181670 , J:188346 )

• 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

short snout ( J:181670 )

• snubbed snout

homeostasis/metabolism

abnormal blood homeostasis ( J:188346 )

• 16-fold elevation in circulating 3-methylglutaconic acid

decreased circulating insulin-like growth factor I level ( J:188346 )

• 80% reduction

decreased body surface temperature ( J:188346 )

• surface body temperature is about 5 degrees C lower than in wild-type

dehydration ( J:181670 )

• despite normal drinking

decreased liver glycogen level ( J:181670 )

abnormal phospholipid level ( J:188346 )

• content of mitochondrial-specific lipid, cardiolipin, and its metabolic precursor, phosphatidylglycerol, is increased by 49 and 92% respectively, in the liver

increased liver triglyceride level ( J:188346 )

• increase in hepatic triglycerol content

• however circulating triglycerol is normal

liver/biliary system

abnormal liver morphology ( J:181670 )

• livers are glycogen depleted compared to in wild-type mice

increased liver weight ( J:188346 )

• liver weight is increased by 30%

decreased liver glycogen level ( J:181670 )

increased liver triglyceride level ( J:188346 )

• increase in hepatic triglycerol content

• however circulating triglycerol is normal

macrovesicular hepatic steatosis ( J:188346 )

• livers show evidence of hepatic steatosis, characterized by large lipid rafts

muscle

abnormal ventricle myocardium morphology ( J:181670 )

• 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

dilated cardiomyopathy ( J:181670 )

skeleton

abnormal epiphyseal plate morphology ( J:188346 )

• 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

abnormal long bone epiphyseal plate proliferative zone ( J:188346 )

• 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		DO ID	OMIM ID(s)	Ref(s)
3-methylglutaconic aciduria type 3		DOID:0110004	OMIM:258501	J:181670 , J:188346