Mouse sulphamidase gene: characterization of the promoter region of the gene and expression in mouse tissues

Abstract

Sulphamidase is a lysosomal enzyme necessary for the degradation of heparan sulphate. The deficiency of this hydrolase causes a disorder known as mucopolysaccharidosis type IIIA, characterized by a profound neurological deterioration. Human and mouse exon-intron structures were reported without any characterization of their promoter regions [DNA Res. 3 (1996) 269; Mamm. Genome 11 (2000) 436]. The promoter region was isolated and characterized to understand the factors affecting the expression of mouse sulphamidase. The 5'-flanking region was shown to contain a GC-rich region and putative binding sites for the transcription factors SRY, MZF1 and Nkx-2.5 with no TATA or CAAT boxes present. The 5' region had promoter activity to drive luciferase gene expression in transfected COS cells. The transcription initiation site of mouse sulphamidase was mapped to a single adenine residue 355 bases upstream of ATG codon. Northern blot analysis revealed differential expression of a major transcript of 4.5 kb in all tissues examined. Finally, the 3'-untranslated region of the mouse sulphamidase gene was isolated and found to be longer than the region identified in the human gene.