title: Single gene defects in mice: the role of voltage-dependent calcium channels in absence models.
abstract: Nineteen genes encoding alpha1, beta, gamma, or alpha2delta voltage-dependent calcium channel subunits have been identified to date. Recent studies have found that three of these genes are mutated in mice with generalised cortical spike-wave discharges (models of human absence epilepsy), emphasising the importance of calcium channels in regulating the expression of this inherited seizure phenotype. The tottering (tg) locus encodes the calcium channel alpha1 subunit gene Cacna1a, lethargic (lh) encodes the beta subunit gene Cacnb4, and stargazer (stg) encodes the gamma subunit gene Cacng2. These calcium channel mutants should provide important insights into the basic mechanisms of neuronal synchronisation, and the genes may be considered candidates for involvement in similar human disorders. The mutant models offer an important opportunity to elucidate the molecular, developmental, and physiological mechanisms underlying one subtype of absence epilepsy. Since calcium channels are involved in numerous cellular functions, including proliferation and differentiation, membrane excitability, neurite outgrowth and synaptogenesis, signal transduction, and gene expression, their role in generating the absence epilepsy phenotype may be complex. A comparative analysis of channel function and neural excitability patterns in tottering, lethargic, and stargazer brain should be useful in identifying the common elements of calcium channel involvement in these absence models.
authors.affiliation: Department of Neurology, Baylor College of Medicine, Houston, TX 77303, USA. dburgess@bcm.tmc.edu
authors.forename: D L
authors.initials: DL
authors.lastname: Burgess
authors.forename: J L
authors.initials: JL
authors.lastname: Noebels
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics*; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000235:genetics*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics*; D010641:Phenotype
chemical_list: D015220:Calcium Channels