To isolate genes potentially involved in the pathogenesis of Down syndrome, we recently performed exon trapping experiments using a series of cosmid clones derived from the DSCR (CBR-D21S55-ERG) and found six exons which have a striking sequence homology with the Drosophila single-minded (sim) gene [Nature Genetics, 10: 9-10 (1995)]. The Drosophila sim gene encodes a transcription factor which regulates the development of central nervous system midline cell lineage, and thus the identification of a human homolog (hSIM) from the DSCR is quite intriguing. We have now isolated SIM cDNA clones from a mouse embryo cDNA library. Mouse SIM protein is highly homologous to human SIM and Drosophila Sim proteins, all contain the basic-helix-loop-helix (bHLH) domain and the PAS domain. In situ hybridization analysis indicated that SIM is expressed in the diencephalon of mouse embryos at the age of 8-9.5 days postcoitum. These results strongly suggest that the newly isolated mammalian SIM homolog functions as a transcriptional regulator which plays a critical role in the development of the central nervous system. The hSIM gene may potentially be involved in the pathogenesis of Down syndrome.
|ジャーナル||Japanese Journal of Human Genetics|
|出版ステータス||Published - 1996|
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