| First Author | Li W | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 8 | Pages | e44230 |
| PubMed ID | 22952933 | Mgi Jnum | J:191648 |
| Mgi Id | MGI:5462275 | Doi | 10.1371/journal.pone.0044230 |
| Citation | Li W, et al. (2012) New ataxic tottering-6j mouse allele containing a Cacna1a gene mutation. PLoS One 7(8):e44230 |
| abstractText | Voltage-gated Ca(2+) (Ca(v)) channels control neuronal functions including neurotransmitter release and gene expression. The Cacna1a gene encodes the alpha1 subunit of the pore-forming Ca(v)2.1 channel. Mice with mutations in this gene form useful tools for defining channel functions. The recessive ataxic tottering-6j strain that was generated in the Neuroscience Mutagenesis Facility at The Jackson Laboratory has a mutation in the Cacna1a gene. However, the effect of this mutation has not been investigated in detail. In this study, mutation analysis shows a base substitution (C-to-A) in the consensus splice acceptor sequence linked to exon 5, which results in the skipping of exon 5 and the splicing of exon 4 directly to exon 6. The effect of this mutation is expected to be severe as the expressed alpha1 subunit protein lacks a significant part of the S4-S5 linker, S5, and part of S5-S6 linker in domain I. Tottering-6j mice display motor dysfunctions in the footprint, rotating rod, and hind-limb extension tests. Although cytoarchitecture of the mutant brains appears normal, tyrosine hydroxylase was persistently expressed in cerebellar Purkinje cells in the adult mutant mice. These results indicate that tottering-6j is a useful model for functional studies of the Ca(v)2.1 channel. |
