TY - JOUR
T1 - Absence epilepsy in tottering mutant mice is associated with calcium channel defects
AU - Fletcher, Colin F.
AU - Lutz, Cathleen M.
AU - O'Sullivan, T. Norene
AU - Shaughnessy, John D.
AU - Hawkes, Richard
AU - Frankel, Wayne N.
AU - Copeland, Neal G.
AU - Jenkins, Nancy A.
N1 - Funding Information:
We thank C. A. Mason and R. Blazeski for invaluable assistance with immunocytochemistry; L. Cleveland, J. D. Dietz, F. L. Dorsey, C. Dunbar, and A. Valenzuela for expert technical assistance; Belinda Harris for providing mutant mice; L. Tessarollo for helpful advice on in situ analysis; S. Ackerman for her cDNA library; F. Qian, U. Kruse, and A. E. Sippel for Nfix probe; and D. Koeller for Gcdh probe. We thank Dr. J. L. Noebels for many valuable discussions. Research was sponsored by the National Cancer Institute, DHHS, under contract with ABL. The contribution by C. M. L. was in partial fulfillment of a Ph.D. dissertation at the University of Maine and was supported by a DOE-EPSCOR fellowship to C. M. L. and an NIH grant and Klingenstein Fellowship to W. N. F. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the United States Government.
PY - 1996/1/15
Y1 - 1996/1/15
N2 - Mutations at the mouse tottering (tg) locus cause a delayed-onset, recessive neurological disorder resulting in ataxia, motor seizures, and behavioral absence seizures resembling petit mal epilepsy in humans. A more severe allele, leaner (tg(la)), also shows a slow, selective degeneration of cerebellar neurons. By positional cloning, we have identified an α(1A) voltage-sensitive calcium channel gene that is mutated in tg and tg(la) mice. The α(1A) gene is widely expressed in the central nervous system with prominent, uniform expression in the cerebellum. α(1A) expression does not mirror the localized pattern of cerebellar degeneration observed in tg(la) mice, providing evidence for regional differences in biological function of α(1A) channels. These studies define the first mutations in a mammalian central nervous system-specific voltage-sensitive calcium channel and identify the first gene involved in absence epilepsy.
AB - Mutations at the mouse tottering (tg) locus cause a delayed-onset, recessive neurological disorder resulting in ataxia, motor seizures, and behavioral absence seizures resembling petit mal epilepsy in humans. A more severe allele, leaner (tg(la)), also shows a slow, selective degeneration of cerebellar neurons. By positional cloning, we have identified an α(1A) voltage-sensitive calcium channel gene that is mutated in tg and tg(la) mice. The α(1A) gene is widely expressed in the central nervous system with prominent, uniform expression in the cerebellum. α(1A) expression does not mirror the localized pattern of cerebellar degeneration observed in tg(la) mice, providing evidence for regional differences in biological function of α(1A) channels. These studies define the first mutations in a mammalian central nervous system-specific voltage-sensitive calcium channel and identify the first gene involved in absence epilepsy.
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U2 - 10.1016/S0092-8674(00)81381-1
DO - 10.1016/S0092-8674(00)81381-1
M3 - Article
C2 - 8929530
AN - SCOPUS:0030584085
SN - 0092-8674
VL - 87
SP - 607
EP - 617
JO - Cell
JF - Cell
IS - 4
ER -