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

Journal Article · Mon Jul 01 00:00:00 EDT 1996 · Genomics

DOI:https://doi.org/10.1006/geno.1996.0332· OSTI ID:466028

Yamaki, Akiko ^[1]; Kudoh, Jun; Shindoh, Nobuaki ^[2]

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1. Keio Univ. School of Medicine, Tokyo (Japan)
2. Keio Univ. School of Medicine, Tokyo (Japan); and others

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 provator 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 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. 36 refs., 6 figs.

• OSTI ID: 466028
• Journal Information: Genomics, Vol. 35, Issue 1; Other Information: PBD: 1 Jul 1996
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
DOWNS SYNDROME
PATHOGENESIS
MAN
HEREDITARY DISEASES
MENTAL DISORDERS
CHROMOSOMES
GENETIC MAPPING
HUMAN CHROMOSOME 21
CHROMOSOMAL ABERRATIONS
TRANSCRIPTION FACTORS
STRUCTURE-ACTIVITY RELATIONSHIPS
GENE REGULATION
DNA-CLONING
DNA SEQUENCING
CENTRAL NERVOUS SYSTEM
ONTOGENESIS
MICE
DROSOPHILA
AMINO ACID SEQUENCE
IN-SITU HYBRIDIZATION
BIOLOGICAL MARKERS
SCANNING ELECTRON MICROSCOPY