J. Biochem, 1998, Vol. 123, No. 6 1055-1063
© 1998 Japanese Biochemical Society
research-article |
Molecular Characterization of the Mouse mtprd Gene, a Homologue of Human TPRD: Unique Gene Expression Suggesting Its Critical Role in the Pathophysiology of Down Syndrome1
*Department of Pharmacology, Tokyo Women's Medical University, School of Medicine 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666
Human Genome Center, Institute of Medical Science, The University of Tokyo Tokyo 108-8639
Department of Biological Sciences, Graduate School of Science, The University of Tokyo Tokyo 113-0033
2To whom correspondence should be addressed. Phone: +81-3-3353-8111 (Ext. 22513), Fax:+81-3-5269-7417, E-mail: fuji{at}research.twmc.ac.jp
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 mouse homologue of TPRD cDNA, mtprd, and examined its expression profile in mouse embryos. The gene was mapped to mouse chromosome 16C3.3–4, consistent with the location of DCR, and encodes 1, 979 amino acid residues 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 those of TPRD. Several splicing variants of the 5' portion of the open reading frame of mtprd were identified by RT-PCR and sequencing of mRNAs. In situ hybridization showed that mtprd is ubiquitously expressed in mouse embryos but predominantly in the central nervous system, including the telencephalon, mesencephalon, and metencephalon. These results suggest that the TPRD gene is one of the genes responsible for not only the morphological anomalies but also the neurological abnormalities observed in Down syndrome. The presence of splicing variants indicates that the protein may also have several isoforms in mice.
1The present work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (No. 08670123), and the H. Yamakawa Scholarship Funds from Tokyo Women's Medical College. The nucleotide sequence data reported in this paper will appear in the DDBJ, EMBL, and GenBank nucleotide sequence databases under accession number AB008516.