PMID- 8661114 OWN - NLM STAT- MEDLINE DCOM- 19960930 LR - 20061115 IS - 0888-7543 (Print) IS - 0888-7543 (Linking) VI - 35 IP - 1 DP - 1996 Jul 1 TI - The mammalian single-minded (SIM) gene: mouse cDNA structure and diencephalic expression indicate a candidate gene for Down syndrome. PG - 136-43 AB - 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. FAU - Yamaki, A AU - Yamaki A AD - Department of Molecular Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 160, Japan. FAU - Noda, S AU - Noda S FAU - Kudoh, J AU - Kudoh J FAU - Shindoh, N AU - Shindoh N FAU - Maeda, H AU - Maeda H FAU - Minoshima, S AU - Minoshima S FAU - Kawasaki, K AU - Kawasaki K FAU - Shimizu, Y AU - Shimizu Y FAU - Shimizu, N AU - Shimizu N LA - eng SI - GENBANK/D64135 SI - GENBANK/D70838 PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Genomics JT - Genomics JID - 8800135 RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (DNA, Complementary) RN - 0 (DNA-Binding Proteins) RN - 0 (Drosophila Proteins) RN - 0 (Fetal Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Nuclear Proteins) RN - 0 (sim protein, Drosophila) SB - IM MH - Animals MH - Base Sequence MH - Basic Helix-Loop-Helix Transcription Factors MH - Cloning, Molecular MH - DNA, Complementary/*genetics MH - DNA-Binding Proteins/biosynthesis/*genetics/physiology MH - Diencephalon/embryology/*metabolism MH - Down Syndrome/*genetics MH - Drosophila Proteins MH - Drosophila melanogaster/genetics MH - Fetal Proteins/biosynthesis/genetics/physiology MH - Gene Expression Regulation, Developmental MH - Gene Library MH - *Genes MH - Helix-Loop-Helix Motifs/genetics MH - Humans MH - In Situ Hybridization MH - Mammals/genetics MH - Mice/*genetics MH - Mice, Inbred ICR MH - Molecular Sequence Data MH - Nerve Tissue Proteins/biosynthesis/*genetics/physiology MH - Nuclear Proteins/biosynthesis/*genetics/physiology MH - Open Reading Frames MH - Sequence Alignment MH - Sequence Homology, Amino Acid MH - Species Specificity EDAT- 1996/07/01 00:00 MHDA- 1996/07/01 00:01 CRDT- 1996/07/01 00:00 PHST- 1996/07/01 00:00 [pubmed] PHST- 1996/07/01 00:01 [medline] PHST- 1996/07/01 00:00 [entrez] AID - S0888-7543(96)90332-8 [pii] AID - 10.1006/geno.1996.0332 [doi] PST - ppublish SO - Genomics. 1996 Jul 1;35(1):136-43. doi: 10.1006/geno.1996.0332.