title: Dramatically different levels of Cacna1a gene expression between pre-weaning wild type and leaner mice.
abstract: Loss of function mutations of the CACNA1A gene, coding for the α1A subunit of P/Q type voltage-gated calcium channel (Ca(V)2.1), are responsible for Episodic Ataxia type 2 (EA2), an autosomal dominant disorder. A dominant negative effect of the EA2 mutated protein, rather than a haploinsufficiency mechanism, has been hypothesised both for protein-truncating and missense mutations. We analysed the cacna1a mRNA expression in leaner mice carrying a cacna1a mutation leading to a premature stop codon. The results showed a very low mutant mRNA expression compared to the wild type allele. Although the mutant mRNA slightly increases with age, its low level is likely due to degradation by nonsense mediated decay, a quality control mechanism that selectively degrades mRNA harbouring premature stop codons. These data have implications for EA2 in humans, suggesting a haploinsufficiency mechanism at least for some of the CACNA1A mutations leading to a premature stop codon.
authors: Istituto di Farmacologia Traslazionale, CNR, Via Fosso del Cavaliere, 00133 Roma, Italy.
authors: Liana
authors: L
authors: Veneziano
authors: Serena
authors: S
authors: Albertosi
authors: Daniela
authors: D
authors: Pesci
authors: Elide
authors: E
authors: Mantuano
authors: Marina
authors: M
authors: Frontali
authors: Carla
authors: C
authors: Jodice
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001259:Ataxia / Q000235:genetics*; D015220:Calcium Channels / Q000235:genetics; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D020907:Calcium Channels, Q-Type / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D018389:Codon, Nonsense / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D057895:Haploinsufficiency / Q000235:genetics; D006801:Humans; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D020125:Mutation, Missense / Q000235:genetics; D009759:Nystagmus, Pathologic / Q000235:genetics*; D014886:Weaning
chemical_list: D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D018389:Codon, Nonsense; C105656:CACNA1A protein, human