Chromosomal location of murine Disabled-2 gene and structural comparison with its human ortholog

Disabled-2 (Dab2) is one of the two mammalian orthologs of the Drosophila D isabled. The three spliced forms, p96, p93, and p67 of murine Dab2 cDNAs we re first isolated as phosphoproteins functioning in the macrophage CSF-1 si gnal transduction pathway. Subsequently, the involvement of Dab2 in ovarian cancer development has been investigated: Dab2 expression is lost or great ly diminished in breast and ovarian cancers, and gene deletions have been f ound. Regulation of Disabled-2 expression is also found to be important in development and physiological functions. Structural information of the muri ne Dab2 gene is essential for studies of transcription regulation and gene function in mouse models. In this study, the mouse Dab2 gene coding sequenc e was identified and sequenced from three lambda phage clones containing th e gene. Two BAC clones of mouse genomic DNA were also used to identify the sequences of the non-coding first exon and promoter. The first exon is sepa rated from the second exon by a large (15 kb) intron. The mouse gene is abo ut 40 kb in size and consists of 15 exons, producing a 3.6 kb message. The translation initiation site resides in the middle of the second exon. The m ouse Dab2 gene structure is very similar to that of its human ortholog in e xon/intron sizes and promoter sequences. The chromosomal localization of mo use Dab2 was mapped by FISH to chromosome 15A2, a site of syntax with the h uman 5p12 a here human Dab2 gene resides. The information on the mouse Dab2 gene structure and promoter will be invaluable in studies of the involveme nt of Dab2 gene in cancer, expression, physiological function, and developm ent in mouse models. (C) 2001 Elsevier Science B.V. All rights reserved.