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.
Letts
V A
VA
The Jackson Laboratory, Bar Harbor, Maine 04609, USA. val@jax.org
Felix
R
R
Biddlecome
G H
GH
Arikkath
J
J
Mahaffey
C L
CL
Valenzuela
A
A
Bartlett
F S
FS
Mori
Y
Y
Campbell
K P
KP
Frankel
W N
WN
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