Calcium channel β4 (CACNB4): Human ortholog of the mouse epilepsy gene lethargic

Andrew Escayg, Julie M. Jones, Jennifer A. Kearney, Peter F. Hitchcock, Miriam H. Meisler*

*Corresponding author for this work

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The mouse neurological mutant lethargic (lh) is characterized by ataxia, focal myoclonus, and absence epilepsy due to a loss-of-function mutation in the β4 subunit of the voltage-gated calcium channel. To evaluate the role of this channel subunit in human neurological disease, we determined the chromosomal location and intron/exon structure of the human CACNB4 gene. The 1560-bp open reading frame of the CACNB4 cDNA predicts a 58-kDa protein with an amino acid sequence that is 99% identical to the rat protein. The 13 coding exons of CACNB4 span >55 kb of genomic DNA. Human cerebellar RNA contains one major CACNB4 transcript that is 9 kb in length. Expression of CACNB4 was detected in cerebellum, kidney, testis, retina, lymphoblasts, and circulating lymphocytes. Retinal transcripts were localized by in situ hybridization to ganglion cells and the inner nuclear layer. Analysis of the GeneBridge 4 radiation hybrid mapping panel localized CACNB4 to position 791 cR on human chromosome 2, in a conserved linkage group on human 2q22-q31 and mouse chromosome 2. We localized CACNB4 to the 1.3-Mb YAC clone 952F10 in Whitehead contig WC861, along with the polymorphic markers D2S2236 and D2S2299. The chromosomal linkage of three of the four β subunit genes to homeobox gene clusters associates the evolutionary origin of the β gene family with the events that generated the four HOX clusters early in vertebrate evolution.

Original languageEnglish (US)
Pages (from-to)14-22
Number of pages9
JournalGenomics
Volume50
Issue number1
DOIs
StatePublished - May 15 1998

Fingerprint

Calcium Channels
Epilepsy
Chromosomes, Human, Pair 2
Genes
Exons
Radiation Hybrid Mapping
Neurologic Mutant Mice
Myoclonic Epilepsy
Absence Epilepsy
Partial Epilepsy
Homeobox Genes
Human Chromosomes
Ataxia
Multigene Family
Ganglia
Introns
Cerebellum
Open Reading Frames
In Situ Hybridization
Vertebrates

ASJC Scopus subject areas

  • Genetics

Cite this

Escayg, Andrew ; Jones, Julie M. ; Kearney, Jennifer A. ; Hitchcock, Peter F. ; Meisler, Miriam H. / Calcium channel β4 (CACNB4) : Human ortholog of the mouse epilepsy gene lethargic. In: Genomics. 1998 ; Vol. 50, No. 1. pp. 14-22.
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Calcium channel β4 (CACNB4) : Human ortholog of the mouse epilepsy gene lethargic. / Escayg, Andrew; Jones, Julie M.; Kearney, Jennifer A.; Hitchcock, Peter F.; Meisler, Miriam H.

In: Genomics, Vol. 50, No. 1, 15.05.1998, p. 14-22.

Research output: Contribution to journalArticle

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