MOUSE CATHEPSIN-D GENE - MOLECULAR-ORGANIZATION, CHARACTERIZATION OF THE PROMOTER, AND CHROMOSOMAL LOCALIZATION

A cloned mouse genomic DNA fragment containing the gene encoding cathe psin D (Catd) encompasses If kb of genomic DNA and is composed of 9 ex ons. Using recombinant inbred strains, we localized the Catd gene on c hromosome 4, tightly linked to the loci Mtv-13, Cyp4a, Ms15-1, and Pmv -19. The exon-intron organization of the Catd gene was shown to be ver y similar to that of its human counterpart. Presence of a CPG island, absence of a TATA box, and initiation of transcription at more than on e site indicate that the Catd gene is a ''housekeeping'' gene. A 1.2-k b fragment containing the 5'-flanking region of the gene displayed pro moter activity in BHK-21 cells. Comparison of the nucleotide sequences of mouse and human cathepsin D promoter regions revealed conservation of three potential regulatory elements: an E box, a GC box and a pote ntial cAMP-responsive element. In contrast to the 5' region of human c athepsin D, the murine gene contains three CCAAT boxes but lacks any o f the four AP2 binding sites found in the human gene.