B6.Cg-Cacna1a^rkr/Mmjax

Stock number: 020653
Product name: rocker
Research areas: Cell Biology Research, Neurobiology Research

Description

Rocker (rkr) mutant mice possess an ENU-induced point mutation in the Cacna1a (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit) gene. Homozygous mice exhibit mild ataxia, absence seizures, and abnormal dendritic branching in Purkinje cells. They may be useful for studies of voltage-dependent calcium channels and as an additional phenotype for the Cacna1a allelic series.

Detailed description

Cacna1a (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit) is expressed in neuronal tissue and encodes the pore-forming alpha1a subunit, which directs activity of the CaV2.1 voltage-gated calcium channel. Mutations in CACNA1A are associated with ataxia and migraines. Mice homozygous for the rocker (rkr) ENU-induced allele exhibit splayed hindlimbs, a mildly ataxic gait, absence seizures, abnormal ocular motor behavior and impaired synaptic transmission in parallel fiber Purkinje cells (PF-PC). Dendrites from Purkinje cells have less arborization, reduced length, and a "weeping willow" appearance. The rocker phenotype is less severe than in other Cacna1a mutants (tottering, leaner). Heterozygotes are viable and fertile. These mutant mice may be useful for studies of voltage-dependent calcium channels and as an additional phenotype for the Cacna1a allelic series.

Development

Male mice from a mixed background were treated with multidose N-ethyl-N-nitrosourea (ENU); in the fourth generation of breeding, ataxic mice were observed. To analyze the mutation these mice were crossed to C57BL/6 mice for five generations. The rocker (rkr) mutation is a C to A transversion at position 3929 of the Cacna1a (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit) gene. The mutation alters the corresponding amino acid from threonine to lysine at amino acid 1310 (T1310K) in an extracellular loop located between transmembrane regions 5 and 6 of the third homologous domain. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Allele

Symbol: Cacna1a^rkr
Name: rocker
MGI accession ID: MGI:2154404
Generation method: Chemically induced (ENU)
Marker symbol: Cacna1a
Marker name: calcium channel, voltage-dependent, P/Q type, alpha 1A subunit
Chromosome: 8
Strain of origin: mixed
Molecular note: A C to A transversion mutation at position 4073 (c.C>A4073) predicts a nonconservative threonine to lysine substitution at position 1358 (p.T1358K) in the extracellular pore-forming loop region that connects segments 5 and 6 of repeat III of the encoded protein.