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

A cloned mouse genomic DNA fragment containing the gene encoding cathepsin D (Catd) encompasses If kb of genomic DNA and is composed of 9 exons. Using recombinant inbred strains, we localized the Catd gene on chromosome 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 very similar to that of its human counterpart. Presence of a CPG island, absence of a TATA box, and initiation of transcription at more than one site indicate that the Catd gene is a ''housekeeping'' gene. A 1.2-kb fragment containing the 5'-flanking region of the gene displayed promoter 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 potential cAMP-responsive element. In contrast to the 5' region of human cathepsin D, the murine gene contains three CCAAT boxes but lacks any of the four AP2 binding sites found in the human gene.