TY - JOUR
T1 - Calcium channel β4 (CACNB4)
T2 - Human ortholog of the mouse epilepsy gene lethargic
AU - Escayg, Andrew
AU - Jones, Julie M.
AU - Kearney, Jennifer A.
AU - Hitchcock, Peter F.
AU - Meisler, Miriam H.
N1 - Funding Information:
We thank Daniel L. Burgess for carrying out the BLAST search that identi®ed IMAGE Clone 29467 and for designing four primers used in this study (BF, BR, DF, and KF). We are grateful to Eric Fearon, Thomas Glaser, and Debra Thompson for providing valuable materials and to Lori Isom and James Offord for comments on the manuscript. Supported by NIH Grants NS34509 to M.H.M., EYO706 to P.F.H. and EY07003 (Core) to P.F.H. Tissue samples were obtained through the Michigan Alzheimers Disease Research Center (P50 AG08671) and the Tissue Procurement Core, Comprehensive Cancer Center (P30 CA46592).
PY - 1998/5/15
Y1 - 1998/5/15
N2 - 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.
AB - 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.
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U2 - 10.1006/geno.1998.5311
DO - 10.1006/geno.1998.5311
M3 - Article
C2 - 9628818
AN - SCOPUS:0032524332
SN - 0888-7543
VL - 50
SP - 14
EP - 22
JO - Genomics
JF - Genomics
IS - 1
ER -
