MOLECULAR CHARACTERIZATION OF THE MOUSE MTPRD GENE, A HOMOLOG OF HUMAN TPRD - UNIQUE GENE-EXPRESSION SUGGESTING ITS CRITICAL ROLE IN THE PATHOPHYSIOLOGY OF DOWN-SYNDROME

We and others recently isolated a human TPRD gene, possessing a motif of the tetratricopeptide repeat (TPR), from the Down syndrome-critical region (DCR) of chromosome 21q22.2. In this study, we isolated a mous e homologue of TPRD cDNA, mtprd, and examined its expression profile i n mouse embryos. The gene was mapped to mouse chromosome 16C3.3-4, con sistent with the location of DCR, and encodes 1,979 amino acid residue s with 76% identity to TPRD, The mtprd protein has three units of the TPR motif with 91% homology to TPRD, The protein also has two regions homologous to several matrix proteins with 86 and 70% identities to th ose of TPRD, Several splicing variants of the 5' portion of the open r eading frame of mtprd were identified by RT-PCR and sequencing of mRNA s, In situ hybridization showed that mtprd is ubiquitously expressed i n mouse embryos but predominantly in the central nervous system, inclu ding the telencephalon, mesencephalon, and metencephalon, These result s suggest that the TPRD gene is one of the genes responsible for not o nly the morphological anomalies but also the neurological abnormalitie s observed in Down syndrome, The presence of splicing variants indicat es that the protein may also have several isoforms in mice.