title: New ataxic tottering-6j mouse allele containing a Cacna1a gene mutation.
abstract: Voltage-gated Ca(2+) (Ca(v)) channels control neuronal functions including neurotransmitter release and gene expression. The Cacna1a gene encodes the α1 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 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 Ca(v)2.1 channel.
authors.affiliation: Bio-X Institutes, Key Laboratory for Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, People's Republic of China. liwd@sjtu.edu.cn
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Tian
authors.forename: Tae Yeon
authors.initials: TY
authors.lastname: Kim
authors.forename: Namiko
authors.initials: N
authors.lastname: Ito
authors.forename: Kaori
authors.initials: K
authors.lastname: Watanabe
authors.forename: Akiko
authors.initials: A
authors.lastname: Tsuji
authors.forename: Kimie
authors.initials: K
authors.lastname: Niimi
authors.forename: Yo
authors.initials: Y
authors.lastname: Aoyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Arai
authors.forename: Eiki
authors.initials: E
authors.lastname: Takahashi
mesh_terms: D000483:Alleles; D000818:Animals; D001259:Ataxia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D001483:Base Sequence; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type / Q000235:genetics*; D020907:Calcium Channels, Q-Type / Q000235:genetics*; D002531:Cerebellum / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D016678:Genome / Q000235:genetics; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000502:physiology; D053580:Muscle Strength / Q000502:physiology; D009154:Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D045442:Rotarod Performance Test; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase