Escayg A, Jones J M, Kearney J A, Hitchcock P F, Meisler M H
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, 48109-0618, USA.
Genomics. 1998 May 15;50(1):14-22. doi: 10.1006/geno.1998.5311.
The mouse neurological mutant lethargic (lh) is characterized by ataxia, focal myoclonus, and absence epilepsy due to a loss-of-function mutation in the beta4 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 beta subunit genes to homeobox gene clusters associates the evolutionary origin of the beta gene family with the events that generated the four HOX clusters early in vertebrate evolution.
小鼠神经学突变体嗜睡（lh）的特征为共济失调、局灶性肌阵挛以及由于电压门控钙通道β4亚基功能丧失突变导致的失神癫痫。为评估该通道亚基在人类神经疾病中的作用，我们确定了人类CACNB4基因的染色体定位以及内含子/外显子结构。CACNB4 cDNA的1560个碱基对的开放阅读框预测出一种58 kDa的蛋白质，其氨基酸序列与大鼠蛋白质的序列有99%的同一性。CACNB4的13个编码外显子跨越超过55 kb的基因组DNA。人类小脑RNA包含一种长度为9 kb的主要CACNB4转录本。在小脑、肾脏、睾丸、视网膜、淋巴母细胞和循环淋巴细胞中检测到了CACNB4的表达。通过原位杂交将视网膜转录本定位到神经节细胞和内核层。对GeneBridge 4辐射杂种图谱板的分析将CACNB4定位到人类染色体2上791 cR的位置，位于人类2q22 - q31和小鼠染色体2上的一个保守连锁群中。我们将CACNB4定位到Whitehead重叠群WC861中的1.3 - Mb YAC克隆952F10上，同时还有多态性标记D2S2236和D2S2299。四个β亚基基因中的三个与同源框基因簇的染色体连锁将β基因家族的进化起源与脊椎动物进化早期产生四个HOX簇的事件联系起来。
