Phenotypes associated with this allele

• Allele Symbol: Cacna1a^tm2.1Kewa
• Allele Name: targeted mutation 2.1, Kei Watase
• Allele ID: MGI:5467732
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cacna1a^tm2.1Kewa/Cacna1a^tm2.1Kewa	B6.Cg-Cacna1a^tm2.1Kewa	MGI:5467734
ht2	Cacna1a^tm2.1Kewa/Cacna1a^+	B6.Cg-Cacna1a^tm2.1Kewa	MGI:5467735
cx3	Cacna1a^tm2.1Kewa/Cacna1a^tm2.1Kewa Ctsb^tm1Jde/Ctsb^tm1Jde	involves: 129P2/OlaHsd * C57BL/6	MGI:5467736
cx4	Cacna1a^tm2.1Kewa/Cacna1a^tm2.1Kewa Ctsb^tm1Jde/Ctsb^+	involves: 129P2/OlaHsd * C57BL/6	MGI:5467737

Genotype
MGI:5467734

hm1

• Allelic Composition: Cacna1a^tm2.1Kewa/Cacna1a^tm2.1Kewa
• Genetic Background: B6.Cg-Cacna1a^tm2.1Kewa

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

behavior/neurological

abnormal motor coordination/balance ( J:190729 )

• impaired performance on the rotarod at 6 weeks of age

ataxia ( J:190729 )

• develop an ataxic gait at 6 weeks of age

• gait progressively deteriorates with age

abnormal gait ( J:190729 )

• wobbling and short stepped gait at 15 weeks of age

short stride length ( J:190729 )

• at 15 weeks of age

cellular

abnormal Purkinje cell mitochondrial morphology ( J:190729 )

nervous system

abnormal Purkinje cell morphology ( J:190729 )

• cytoplasmic inclusions are detected in the cerebellum at 7 weeks of age and become more evident with age

• inclusions colocalize with lysosomal markers

• at 15 weeks of age remaining cells have irregularly shaped nuclei and contain many structurally abnormal mitochondria

abnormal Purkinje cell mitochondrial morphology ( J:190729 )

Purkinje cell degeneration ( J:190729 )

• steep decline in cell numbers after 6 weeks of age

abnormal Purkinje cell dendrite morphology ( J:190729 )

• decrease in dendritic arborization and numerous axonal swellings are seen

decreased Purkinje cell size ( J:190729 )

• cell bodies appear smaller at 6 weeks of age

abnormal nervous system electrophysiology ( J:190729 )

• in brain slices containing Purkinje cells injection of a small depolarizing current fails to induce an oscillating behavior in the Na+ spike bursts which is seen in some (4 of 18 slices) wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
spinocerebellar ataxia type 6		DOID:0050956	OMIM:183086	J:190729

Genotype
MGI:5467735

ht2

• Allelic Composition: Cacna1a^tm2.1Kewa/Cacna1a⁺
• Genetic Background: B6.Cg-Cacna1a^tm2.1Kewa

behavior/neurological

abnormal motor coordination/balance ( J:190729 )

• impaired performance on the rotarod at 18 months of age

ataxia ( J:190729 )

• develops at about 1 year of age

nervous system

Purkinje cell degeneration ( J:190729 )

• cell loss is detected at 100 weeks of age

• cytoplasmic inclusions are detected in the cerebellum after 15 weeks of age and become more evident with age

Genotype
MGI:5467736

cx3

• Allelic Composition: Cacna1a^tm2.1Kewa/Cacna1a^tm2.1Kewa; Ctsb^tm1Jde/Ctsb^tm1Jde
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

behavior/neurological

abnormal motor coordination/balance ( J:190729 )

• impaired performance on the rotarod at 9 weeks of age

• performance is worse than in mice homozygous for Cacna1a^tm2.1Kewa alone

nervous system

abnormal Purkinje cell morphology ( J:190729 )

• significant increase in the percentage of cells harboring cytoplasmic inclusions at 5 weeks of age compared to mice homozygous for Cacna1a^tm2.1Kewa alone

Purkinje cell degeneration ( J:190729 )

• marked loss of cells at 9 weeks of age most prominently in the anterior lobe

• loss is more severe than in mice homozygous for Cacna1a^tm2.1Kewa alone

Genotype
MGI:5467737

cx4

• Allelic Composition: Cacna1a^tm2.1Kewa/Cacna1a^tm2.1Kewa; Ctsb^tm1Jde/Ctsb⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

behavior/neurological

abnormal motor coordination/balance ( J:190729 )

• impaired performance on the rotarod at 9 weeks of age

• performance is worse than in mice homozygous for Cacna1a^tm2.1Kewa alone