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

Verity A. Letts, Ricardo Felix, Gloria H. Biddlecome, Jyothi Arikkath, Connie L. Mahaffey, Alicia Valenzuela, Frederick S. Bartlett, Yasuo Mori, Kevin P. Campbell, Wayne N. Frankel

Research output: Contribution to journalArticlepeer-review

473 Scopus citations


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 (Ca2+) channels. Stargazin is brain-specific and, like other neuronal Ca2+-channel subunits, is enriched in synaptic plasma membranes. In vitro, stargazin increases steady-state inactivation of α1 class A Ca2+ channels. The anticipated effect in stargazer mutants, inappropriate Ca2+ entry, may contribute to their more pronounced seizure phenotype compared with other mouse absence models with Ca2+-channel defects. The discovery that the stargazer gene encodes a γ subunit completes the identification of the major subunit types for neuronal Ca2+ channels, namely α1, α2δ, 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.

Original languageEnglish (US)
Pages (from-to)340-347
Number of pages8
JournalNature Genetics
Issue number4
StatePublished - 1998

ASJC Scopus subject areas

  • Genetics


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