To isolate genes potentially involved in the pathogenesis of Down syndrome, we have performed exon trapping for the "Down syndrome critical region". We have isolated over 100 exons including those from known human genes and homologs of Drosophila singleminded (sim) and minibrain (mnb) genes. These genes locate in the order of cen-SIM2HCS-TPRD-MNB-KCNJ6-ERG-tel. Drosophila sim and mnb genes are required for development of central nervous system. The structural characteristics of human and mouse SIM2 proteins that contain bHLH and PAS domains and expression in the diencephalon during mouse embryogenesis strongly suggest that SIM proteins function as a transcriptional regulator in the development of the central nervous system. Human MNB cDNA encodes a protein kinase with a nuclear targeting signal and a catalytic domain highly homologous to Drosophila mnb protein kinase and strikingly resembles the rat Dyrk protein kinase with a dual specificity. The MNB mRNA is expressed in various tissues including fetal and adult brains. These results implicate that human MNB protein may play a significant role in a signaling pathway regulating nuclear functions of neuronal cell proliferation, contributing to certain features of Down syndrome.
|ジャーナル||Japanese Journal of Human Genetics|
|出版ステータス||Published - 1997 12月 1|
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