STRUCTURE OF THE MOUSE DIPEPTIDYL PEPTIDASE-IV (CD26) GENE

Dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5) is an ectopeptidase whos e expression is modulated during thymocyte differentiation and T cell activation. We describe here the organization of the mouse DPP IV gene . This gene, which encompasses more than 90 kb, is composed of 26 exon s separated by introns, the lengths of which vary from 100 bp to more than 20 kb. Reverse PCR performed on RNA from different tissues indica ted that DPP IV transcripts do not contain alternatively spliced CDS s equences and, therefore, are supposed to yield a single polypeptide. H owever, two types of specific mRNA have been detected that differ in t heir 3'UTR sequences. They derive from alternative polyadenylation of the DPP IV primary transcript, since the different 3'UTR sequences are contiguous in the mouse DPP IV gene. Sequence analysis of the gene 5' -flanking region revealed several structural features found in the TAT AA-box-less promoters, including a G+C-rich segment, a high frequency of dinucleotide CpG, and an imperfect symmetrical dyad. The DPP IV gen e was assigned by in situ hybridization to the mouse [2C2-2D] region, which is syntenic with human chromosome 2. These data indicate that th e human Dpp4 locus is located within this synteny region (i.e., 2q14-q 37). The genomic organization of the mouse DPP IV gene is compared to that of classical serine proteases and serine hydrolases. As structura l and mechanistic conservation in the absence of sequence similarity i s the most remarkable feature among alpha/beta hydrolases [Ollis, D. L ., et al. (1992) Protein Eng. 5, 197-211], we report the possible evol utionary link between the DPP IV related family and alpha/beta hydrola ses.