STRUCTURAL ORGANIZATION AND EXPRESSION OF THE GENE FOR THE MOUSE G(M2) ACTIVATOR PROTEIN

The G(M2) activator protein is an essential component for the degradat ion of G(M2) ganglioside by hexosaminidase A in vivo. Mutations in the human gene coding for the G(M2) activator protein cause the AB varian t of G(M2)-gangliosidosis, a condition that is clinically indistinguis hable from Tay-Sachs disease. To understand better factors affecting t he expression of the G(M2) activator protein gene (Gm2a) in mouse tiss ues, we have determined its exon-intron organization and analyzed its promoter region. Gm2a is about 14 kb, has four exons, and the 5' flank ing region contains a CAAT box, Sp1 binding sites, AP-1, AP-2 sites, a nd 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. Similarit ies between the elements present in Gm2a and Hexa promoters might in p art explain their similar expression patterns in mouse tissues. The di fferent levels of G(M2) 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 demonst rated variation in the G(M2) activator protein mRNA expression during mouse development. Gm2a was mapped to Chromosome (Chr) 11, where it co -segregated with Csfgm.