PubMed 17146767

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav2.1

Title: Conditional inactivation of the Cacna1a gene in transgenic mice.

Authors: Boyan Todorov, Rob C G Van De Ven, Simon Kaja, Ludo A M Broos, Sjef J Verbeek, Jaap J Plomp, Michel D Ferrari, Rune R Frants, Arn M J M Van Den Maagdenberg

Journal, date & volume: Genesis, 2006 Dec , 44, 589-94

PubMed link:

Ca(v)2.1 (P/Q-type) voltage-gated calcium channels play an important role in neurotransmitter release at many brain synapses and at the neuromuscular junction. Mutations in the CACNA1A gene, encoding the pore forming alpha(1) subunit of Ca(v)2.1 channels, are associated with a wide spectrum of neurological disorders. Here we generated mice with a conditional, floxed, Cacna1a allele without any overt phenotype. Deletion of the floxed Cacna1a allele resulted in ataxia, dystonia, and lethality during the fourth week, a severe phenotype similar to conventional Ca(v)2.1 knockout mice. Although neurotransmitter release at the neuromuscular junction was not affected in the conditional mice, homozygous deletion of the floxed allele caused an ablation of Ca(v)2.1 channel-mediated neurotransmission that was accompanied by a compensatory upregulation of Ca(v)2.3 (R-type) channels at this synapse. Pharmacological inhibition of Ca(v)2.1 channels is possible, but the contributing cell-types and time windows relevant to the different Ca(v)2.1-related neurological disorders can only be reliably determined using Cacna1a conditional mice.