Phenotypes Associated with This Genotype

Genotype
MGI:3706704

• Allelic Composition: Cacna1a^Wb/Cacna1a^Wb
• Genetic Background: either: C3.B6-Cacna1a^Wb or (involves: C3H/HeJ * C57BL/6J)

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

mortality/aging

premature death ( J:119639 )

• mice homozygous for this mutation die of starvation at about postnatal day (P)28 unless special provisions are made for their access to food and water

growth/size/body

decreased body size ( J:119639 )

• by P8 homozygous mutant mice are noticeably smaller than their heterozygous or wild-type littermates

behavior/neurological

behavior/neurological phenotype ( J:119639 )

N • neither heterozygous nor homozygous mutant mice exhibit paroxysmal dyskinesia or motor seizure as occurs in mice homozygous for some recessive mutations at this locus

impaired righting response ( J:119639 )

• by P8, homozygous mutant mice have obvious difficulty righting themselves

dystonia ( J:119639 )

• by P21, homozygous mutant mice exhibit symptoms of dystonia

ataxia ( J:119639 )

• by P21, mice homozygous for this mutation exhibit severe ataxia and often lie on their sides with their limbs extended stiffly

• the severity of motor abnormalities in these mutant mice does not progress with age

impaired coordination ( J:119639 )

• motor function testing demonstrates more severe motor function deficits in homozygous than in heterozygous mutant mice

• in the hindlimb extension reflex test, homozygous mutants exhibit spasmodic movements and flexion of the hindlimbs

• the inclined-plane performance of homozygous mutant mice is poor

• in the rotarod test, homozygous mutant mice cannot maintain purchase on even a stationary rod

• the severity of motor abnormalities in these mutant mice does not progress with age

impaired fine motor coordination ( J:119639 )

• in the narrow-beam cross, homozygous mutant mice are unable to cross a narrow beam toward a platform, indicating poor fine motor control

decreased grip strength ( J:119639 )

• the grip strength of homozygous mutant mice is significantly weaker than that of wild-type controls

muscle

dystonia ( J:119639 )

• by P21, homozygous mutant mice exhibit symptoms of dystonia

nervous system

nervous system phenotype ( J:119639 )

N • cerebellar sections show neither Purkinje cell loss nor a decrease in the size of the granule cell layer in heterozygous or homozygous mutant mice

thin cerebellar molecular layer ( J:119639 )

• the molecular layer of the cerebellum in sections from 8 week-old homozygous and heterozygous mutant mice is significantly reduced in thickness and total area relative to that of wild-type control mice

cerebellum atrophy ( J:119639 )

• brain MRI of 8-week-old mutant mice reveals significant cerebellar atrophy, primarily in the superior and medial regions, including lobes III and V; the cerebellum-to-brain volume ratio of homozygous mutants is 17% lower than that of wild-type controls (P<0.01)