The mammalian single-minded (SIM) gene: Mouse cDNA structure and diencephalic expression indicate a candidate gene for Down syndrome

Akiko Yamaki, Setsuko Noda, Jun Kudoh, Nobuaki Shindoh, Hideto Maeda, Shinsei Minoshima, Kazuhiko Kawasaki, Yoshiko Shimisu, Nobuyoshi Shimizu

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Abstract

We have recently isolated a human homolog (hSIM) of the Drosophila single-minded (sim) gene from the Down syndrome critical region of chromosome 21 using the exon trapping method. The Drosophila sim gene encodes a transcription factor that regulates the development of the central nervous system midline cell lineage. To elucidate the structure of the mammalian SIM protein, we have isolated cDNA clones from a mouse embryo cDNA library. The cDNA clones encode a polypeptide of 657 amino acids with a bHLH (basic- helix-loop-helix) domain, characteristic of a large family of transcription factors, and a PAS (Per-Arnt-Sim) domain in the amino-terminal half region. Both of these domains have striking sequence homology with human SIM and Drosophila SIM proteins. In contrast, the carboxy-terminal half of the mouse SIM protein consists of a proline-rich region with no sequence homology to the Drosophila SIM protein. A similar proline-rich domain is known for the activator domain of a number of transcription factors. Whole-mount embryo in situ hybridization experiments revealed that the SIM mRNA is expressed prominently in the diencephalon of mouse embryos at 8-9.5 days postcoitum. The structural characteristics of the mouse SIM protein and its expression in the diencephalon during embryogenesis strongly suggest that the newly isolated mammalian SIM homolog may play a critical role in the development of the mammalian central nervous system. We propose that the human SIM gene may be one of the pathogenic genes of Down syndrome.

Original languageEnglish
Pages (from-to)136-143
Number of pages8
JournalGenomics
Volume35
Issue number1
DOIs
Publication statusPublished - 1996 Jul 1

ASJC Scopus subject areas

  • Genetics

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    Yamaki, A., Noda, S., Kudoh, J., Shindoh, N., Maeda, H., Minoshima, S., Kawasaki, K., Shimisu, Y., & Shimizu, N. (1996). The mammalian single-minded (SIM) gene: Mouse cDNA structure and diencephalic expression indicate a candidate gene for Down syndrome. Genomics, 35(1), 136-143. https://doi.org/10.1006/geno.1996.0332