New Ataxic Tottering-6j Mouse Allele Containing a Cacna1a Gene MutationReportar como inadecuado

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Voltage-gated Ca2+ Cav channels control neuronal functions including neurotransmitter release and gene expression. The Cacna1a gene encodes the α1 subunit of the pore-forming Cav2.1 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 α1 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 Cav2.1 channel.

Autor: Weidong Li , Ying Zhou , Xiaoli Tian , Tae Yeon Kim, Namiko Ito, Kaori Watanabe, Akiko Tsuji, Kimie Niimi, Yo Aoyama, Takashi Ara



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