Molecular characterization of the mouse mtprd gene, a homologue of human TPRD: Unique gene expression suggesting its critical role in the pathophysiology of Down syndrome

Fujiko Tsukahara, Ikuko Urakawa, Masahira Hattori, Momoki Hirai, Ken Ichi Ohba, Toshimasa Yoshioka, Yoshiyuki Sakaki, Takamura Muraki

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Abstract

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 1979 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.

Original languageEnglish
Pages (from-to)1055-1063
Number of pages9
JournalJournal of Biochemistry
Volume123
Issue number6
Publication statusPublished - 1998 Jun
Externally publishedYes

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Keywords

  • Down syndrome
  • mtprd gene
  • Tetratricopeptide repeat
  • TPRD gene

ASJC Scopus subject areas

  • Biochemistry

Cite this

Tsukahara, F., Urakawa, I., Hattori, M., Hirai, M., Ohba, K. I., Yoshioka, T., Sakaki, Y., & Muraki, T. (1998). Molecular characterization of the mouse mtprd gene, a homologue of human TPRD: Unique gene expression suggesting its critical role in the pathophysiology of Down syndrome. Journal of Biochemistry, 123(6), 1055-1063.