Phenotypes Associated with This Genotype

Genotype
MGI:6359449

• Allelic Composition: Coq8a^tm1.1Ics/Coq8a^tm1.1Ics
• Genetic Background: involves: 129S2/SvPas * C57BL/6J * C57BL/6N

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

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:249129 )

• mice show increased seizure susceptibility after pentylenetetrazole injection

abnormal spatial reference memory ( J:249129 )

• mice show a slight delay in spatial memory in the Morris water maze test

ataxia ( J:249129 )

• mice show an increase in nonlinear movement in footprint analysis by 10 weeks of age

• mice develop cerebellar ataxia

impaired coordination ( J:249129 )

• mice develop a progressive loss of coordination after birth

• mice show decreased performance on the accelerating rotarod by 10 weeks of age and a decrease in hindlimb coordination on the beam test that worsens with age

impaired exercise endurance ( J:249129 )

• the maximum speed reached by mice is decreased and mice show a trend toward lower endurance on the accelerating treadmill indicating mild exercise intolerance

• however, muscle strength in the grip test is normal

environmentally induced seizures ( J:249129 )

• mice develop occasional seizures during daily manipulation

homeostasis/metabolism

impaired exercise endurance ( J:249129 )

• the maximum speed reached by mice is decreased and mice show a trend toward lower endurance on the accelerating treadmill indicating mild exercise intolerance

• however, muscle strength in the grip test is normal

hyperlipidemia ( J:249129 )

abnormal enzyme/coenzyme level ( J:249129 )

• 7 month old mice show Coenzyme Q deficiencies in kidney, liver, and skeletal muscle but normal levels in cerebella

muscle

abnormal skeletal muscle morphology ( J:249129 )

• skeletal muscle shows abnormal mitochondria with broken or collapsed cristae and mild fiber degeneration in 7 month old mice

• however, mtDNA levels, cellular respiration, and metabolites of central carbon metabolism are within wild-type ranges

skeletal muscle fiber degeneration ( J:249129 )

• 7 month old mice show mild skeletal muscle fiber degeneration

nervous system

increased susceptibility to pharmacologically induced seizures ( J:249129 )

• mice show increased seizure susceptibility after pentylenetetrazole injection

environmentally induced seizures ( J:249129 )

• mice develop occasional seizures during daily manipulation

abnormal Purkinje cell morphology ( J:249129 )

• most Purkinje cells exhibit a dilated and fragmented Golgi apparatus and dilated cisternae of ribosome-rich endoplasmic reticulum

• however, mitochondria in Purkinje cells appear structurally normal

Purkinje cell degeneration ( J:249129 )

• mice show a defect in the cerebellar Purkinje cell layer, with the presence of dark shrunken neurons and patches of gaps in calbinding staining suggesting neuronal degeneration

• about 10% of Purkinje cells are dark and shrunken with dysmorphic nuclei and abnormal membrane structures

• however, no cerebellar atrophy is seen

abnormal nervous system electrophysiology ( J:249129 )

• Purkinje cells have altered pacemaker activity, with a progressive phenotype showing an increase in interspike interval and normal coefficient of variation between adjacent spikes at 3 months and normal interspike interval but increased coefficient of variation between adjacent spikes at 8 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
primary coenzyme Q10 deficiency 4		DOID:0070241	OMIM:612016	J:249129