Bertoni C, Appolloni M G, Stirling J L, Li S C, Li Y T, Orlacchio A, Beccari T
Dipartimento di Biologia Cellulare e Molecolare, Università di Perugia, Italy.
Mamm Genome. 1997 Feb;8(2):90-3.
The GM2 activator protein is an essential component for the degradation of GM2 ganglioside by hexosaminidase A in vivo. Mutations in the human gene coding for the GM2 activator protein cause the AB variant of GM2-gangliosidosis, a condition that is clinically indistinguishable from Tay-Sachs disease. To understand better factors affecting the expression of the GM2 activator protein gene (Gm2a) in mouse tissues, we have determined its exon-intron organization and analyzed its promoter region. Gm2a is about 14 kb, has four exons, and the 5' flanking region contains a CAAT box, Sp1 binding sites, AP-1, AP-2 sites, and a pair of IRE sites. A 1.2-kb fragment upstream from the initiation codon was shown to have promoter activity in NIH 3T3 cells. Similarities between the elements present in Gm2a and Hexa promoters might in part explain their similar expression patterns in mouse tissues. The different levels of GM2 activator protein mRNA in liver, kidney, brain, and testis are not owing to the use of different transcription start sites, because a single start site was found 50 bp upstream from the initiation codon in each these tissues. Northern blot analysis demonstrated variation in the GM2 activator protein mRNA expression during mouse development. Gm2a was mapped to Chromosome (Chr) 11, where it co-segregated with Csfgm.
GM2激活蛋白是体内己糖胺酶A降解GM2神经节苷脂的必需成分。编码GM2激活蛋白的人类基因突变会导致GM2神经节苷脂贮积症的AB变异型，这种病症在临床上与泰-萨克斯病无法区分。为了更好地了解影响小鼠组织中GM2激活蛋白基因（Gm2a）表达的因素，我们确定了其外显子-内含子结构并分析了其启动子区域。Gm2a约14 kb，有四个外显子，5'侧翼区域包含一个CAAT盒、Sp1结合位点、AP-1、AP-2位点和一对IRE位点。起始密码子上游1.2 kb的片段在NIH 3T3细胞中显示具有启动子活性。Gm2a和Hexa启动子中存在的元件之间的相似性可能部分解释了它们在小鼠组织中的相似表达模式。肝脏、肾脏、大脑和睾丸中GM2激活蛋白mRNA水平的差异并非由于使用了不同的转录起始位点，因为在这些组织中每个组织的起始密码子上游50 bp处都发现了一个单一的起始位点。Northern印迹分析表明，GM2激活蛋白mRNA表达在小鼠发育过程中存在差异。Gm2a被定位到11号染色体（Chr），它与Csfgm共分离。
