Phenotypes Associated with This Genotype

Genotype
MGI:3511770

• Allelic Composition: Ppargc1a^tm1Brsp/Ppargc1a^tm1Brsp
• Genetic Background: involves: 129/Sv * C57BL/6 * FVB/N

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:93896 )

• homozygotes die when exposed to 4^oC for more than 6 hours

postnatal lethality, incomplete penetrance ( J:93896 )

• about 50% of homozygotes die during the postnatal period

adipose tissue

abnormal brown adipose tissue morphology ( J:93896 )

• abundant, large lipid droplets are seen in the brown fat

behavior/neurological

anhedonia ( J:213551 )

• mice exhibit decreased sucrose consumption as compared to wild-type mice

• sucrose consumption is decreased further following administration of kynurenine (KYN)

increased startle reflex ( J:93896 )

• an exaggerated startle response is seen

limb grasping ( J:93896 )

dystonia ( J:93896 )

• dystonic posturing is seen

hyperactivity ( J:93896 )

• a 40% increase in the frequency of random movements is seen

myoclonus ( J:93896 )

• stimulus induced myoclonus is seen

cellular

abnormal cellular respiration ( J:93896 )

• respiration due to mitochondrial proton leak is increased 20% in primary hepatocytes

homeostasis/metabolism

decreased susceptibility to diet-induced obesity ( J:93896 )

• on a high fat diet homozygous mutants are significantly leaner compared to wild-type mice

impaired adaptive thermogenesis ( J:93896 )

• mutants are unable to maintain body temperature in response to cold temperatures developing lethal hypothermia when exposed to 4^oC for more than 6 hours

increased oxygen consumption ( J:93896 )

• total oxygen consumption is increased 17% in primary hepaotcytes

• on a high fat diet oxygen consumption is increased 23% compared to wild-type mice

abnormal glucose homeostasis ( J:93896 )

hypoglycemia ( J:93896 )

• fasted mutants develop mild hypoglycemia after 24 hours

decreased circulating insulin level ( J:93896 )

• fed but not fasted mutants have decreased insulin levels relative to fed or fasted wild-type mice, respectively

abnormal gluconeogenesis ( J:93896 )

• conversion of pyruvate into glucose is reduced following intraperitoneal pyruvate injection

improved glucose tolerance ( J:93896 )

• on a high fat diet homozygous mutants have significantly increased glucose tolerance compared to wild-type mice

increased insulin sensitivity ( J:93896 )

• on a high fat diet homozygous mutants have significantly increased insulin sensitivity compared to wild-type mice

abnormal lipid homeostasis ( J:93896 )

decreased liver triglyceride level ( J:93896 )

• triglyceride levels are lower in the livers of fasted mutant mice

muscle

dystonia ( J:93896 )

• dystonic posturing is seen

myoclonus ( J:93896 )

• stimulus induced myoclonus is seen

nervous system

myoclonus ( J:93896 )

• stimulus induced myoclonus is seen

gliosis ( J:93896 )

• gliosis is seen associated with the spongiform lesions

abnormal neuron morphology ( J:93896 )

• striatal neurons with reduced branches of neurites and occasional vacuoles within the neurons are seen

spongiform encephalopathy ( J:93896 )

• spongiform lesions are seen predominantly in the striatum and to a lesser extent in the cortex

• the lesions are mostly associated with the white matter

growth/size/body

decreased susceptibility to diet-induced obesity ( J:93896 )

• on a high fat diet homozygous mutants are significantly leaner compared to wild-type mice

liver/biliary system

decreased liver triglyceride level ( J:93896 )

• triglyceride levels are lower in the livers of fasted mutant mice