title: Protein expression pattern in cerebellum of Cav2.1 mutant, tottering-6j mice.
abstract: Neuronal voltage-gated Cav2.1 channel controls a broad array of functions, including neurotransmitter release, neuronal excitability, activity-dependent gene expression, and neuronal survival. The Cav2.1 channel is molecular complexes consisting of several subunits: α1, α2/δ, β, and γ. The pore-forming subunit, α1, is encoded by the Cacna1a gene. Tottering-6j mice, generated by the Neuroscience Mutagenesis Facility at The Jackson Laboratory, are a recessive mutant strain in which the mutation has been chemically induced by ethylnitrosourea. In tottering-6j mice, mutation in the Cacna1a gene results in a base substitution (C-to-A) in the consensus splice acceptor sequence, which results in deletion of a part of the S4-S5 linker, S5, and a part of S5-S6 linker domain I in the α1 subunit of Cav2.1 channel. The mice display motor dysfunctions and absence-like seizures. However, protein expression in the cerebellum of tottering-6j mice has not been investigated. Real-time quantitative reverse transcription polymerase chain reaction and histological analyses of the cerebellum of tottering-6j mice revealed high expression levels of tyrosine hydroxylase, zebrin II, and ryanodine receptor 3 compared with those of wild-type mice. Conversely, a low level of calretinin expression was found compared with wild-type mice. These results indicate that Cacna1a mutation plays a significant role in protein expression patterns and that the tottering-6j mouse is a useful model for understanding protein expression mechanisms.
authors.affiliation: Research Resources Center, RIKEN Brain Science Institute 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Tae Yeon
authors.initials: TY
authors.lastname: Kim
authors.forename: Kimie
authors.initials: K
authors.lastname: Niimi
authors.forename: Eiki
authors.initials: E
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D064032:Calbindin 2 / Q000235:genetics / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000235:genetics* / Q000502:physiology*; D002531:Cerebellum / Q000378:metabolism*; D015870:Gene Expression; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D023421:Models, Animal; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics* / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000378:metabolism*
chemical_list: D064032:Calbindin 2; D020864:Calcium Channels, N-Type; D009419:Nerve Tissue Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D014446:Tyrosine 3-Monooxygenase; C071871:zebrin II