Structure and promoter analysis of murine CAD and ICAD genes

Caspase-activated DNase (CAD) degrades chromosomal DNA during apoptosis, wh ereas ICAD (inhibitor of CAD) inhibits the CAD's DNase by binding to it. He re, we describe the assignment of murine CAD and ICAD genes to the distal p art of murine chromosome 4, Molecular cloning and structural analysis indic ated that CAD and ICAD genes are comprised of 7 and 6 exons, respectively. Two different ICAD mRNAs coding for two forms of ICAD proteins (ICAD-S and ICAD-L) were found to be produced by alternative splicing of intron 5. The CAD and ICAD mRNAs were detected ubiquitously in various murine tissues. An alyses of the promoter activity with a series of deletion mutants of their 5' flanking regions indicated that a 190-bp 5' flanking region of the CAD g ene was sufficient to promote the transcription. Whereas, a 120-bp flanking region of ICAD gene was required to promote its transcription. These regio ns do not show similarity between CAD and ICAD genes, suggesting that expre ssion of CAD and ICAD genes is regulated by different mechanisms.