The mouse stargazer gene encodes a neuronal Ca2+-channel gamma 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 gamma 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 alpha1 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 gamma subunit completes the identification of the major subunit types for neuronal Ca2+ channels, namely alpha1, alpha2delta, beta and gamma, 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.
The Jackson Laboratory, Bar Harbor, Maine 04609, USA. val@jax.org
V A
VA
Letts
R
R
Felix
G H
GH
Biddlecome
J
J
Arikkath
C L
CL
Mahaffey
A
A
Valenzuela
F S
FS
Bartlett
Y
Y
Mori
K P
KP
Campbell
W N
WN
Frankel
D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D015220:Calcium Channels / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D004832:Epilepsy, Absence / Q000235:genetics*; D005786:Gene Expression Regulation; D005796:Genes / Q000235:genetics*; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry* / Q000502:physiology; D009928:Organ Specificity; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000032:analysis; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013570:Synaptic Membranes / Q000737:chemistry
C113940:Cacng2 protein, mouse; D015220:Calcium Channels; D012333:RNA, Messenger