Promoter characterization and structure of the gene encoding mouse lysosomal alpha-d-mannosidase

Mouse lysosomal alpha-d-mannosidase (EC 3.2.1.24) is an enzyme involved in the catabolism of N-linked glycoproteins. The gene is differentially expressed in mouse tissues, and the highest level of mRNA is found in the epididymis. The expression of mannosidase in the epididymis may be hormonally regulated, since its activity increases with age. To understand the factors affecting the expression of mouse mannosidase, we isolated and characterized the promoter and determined the exon-intron structure. The gene is about 15 kb, consists of 24 exons, and the 5' flanking region contains GC-rich regions, TATA boxes, CAAT boxes, and putative binding sites for the transcription factors Sp1, AP2, and PEA3. PEA3 factor may participate in the transcriptional control of mannosidase expression in the mouse epididymis. In fact, it has been demonstrated that the PEA3 motif is spatially and temporally expressed within the mouse epididymis, and its accumulation is controlled by androgens and testicular factors. A 1279-bp fragment from the initiation codon had the strongest promoter activity, and three different transcription start sites were identified at positions -131, -149, and -174.