The mouse stargazer gene encodes a neuronal Ca2+-channel γ subunit

Stargazer mice have spike-wave seizures characteristic of absence epilepsy, with accompanying defects in the cerebellum and inner ear. We describe here a novel gene, Cacng2 , whose expression is disrupted in two stargazer alleles. It encodes a 36-kD protein (stargazin) with structural similarity to the γ subunit of skeletal muscle voltage-gated calcium (Ca 2+ ) channels. Stargazin is brain-specific and, like other neuronal Ca 2+ -channel subunits, is enriched in synaptic plasma membranes. In vitro , stargazin increases steady-state inactivation of α 1 class A Ca 2+ channels. The anticipated effect in stargazer mutants, inappropriate Ca 2+ entry, may contribute to their more pronounced seizure phenotype compared with other mouse absence models with Ca 2+ -channel defects. The discovery that the stargazer gene encodes a γ subunit completes the identification of the major subunit types for neuronal Ca 2+ channels, namely α 1 , α 2 δ, β and γ, providing a new opportunity to understand how these channels function in the mammalian brain and how they may be targeted in the treatment of neuroexcitability disorders.