α-Galactosidase A (α-d-galactoside galactohydrolase, EC 220.127.116.11;αGalA) is a lysosomal enzyme that hydrolyses the α-d-galactosyl residues from glycosphingolipids. Fabry disease, an inherited X-linked recessive human metabolic disorder, results from a mutation in the αGalA gene at Xq22. As a prerequisite for generating a mouse model of Fabry disease by gene targeting, we have isolated and characterized the mouse αGalA gene and cDNA. A cloned mouse αGalA cDNA encoded a putative precursor protein of 419 amino acids (aa), including a 31-aa signal peptide (SP). The deduced aa sequence showed high homology (79%) with the human αtGalA protein. Nucleotide sequence analysis of genomic clones revealed that the overall structure and organization of the gene was very similar to that of human αGalA. All exon-intron splice junctions conformed to the GT/AG consensus sequence. Comparison of genomic and cDNA sequences revealed the ocurrence of two putative polyadenylation signals whose alternative use results in the two mouse αGalA transcripts of 1.4 and 3.6 kb. The 5′-flanking region of mouse αGalA had no typical TATA box. Several putative promoter-associated elements including Spl, AP1 and a potential cAMP-responsive element (CRE) were identified. Northern blot analysis revealed the widespread tissue distribution of mouse αGalA transcripts. Lower expression levels, however, were observed in some tissues, implying tissue-specific differences in αGalA promoter function.
|出版ステータス||Published - 1995 12月 12|
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