Characterization ofmsim,a Murine Homologue of theDrosophila simTranscription Factor

Mutations in theDrosophila single-minded(sim) gene result in loss of precursor cells that give rise to midline cells of the embryonic central nervous system. During the course of an exon-trapping strategy aimed at identifying transcripts that contribute to the etiology and pathophysiology of Down syndrome, we identified a human exon from the Down syndrome critical region showing significant homology to theDrosophila simgene. Using a cross-hybridization approach, we have isolated a murine homolog of theDrosophila simgene, which we designatedmsim.Nucleotide and predicted amino acid sequence analyses ofmsimcDNA clones indicate that this gene encodes a member of the basic–helix–loop–helix class of transcription factors. The murine andDrosophilaproteins share 88% residues within the basic–helix–loop–helix domain, with an overall homology of 92%. In addition, the N-terminal domain of MSIM contains two PAS dimerization motifs also featured in theDrosophila simgene product, as well as a small number of other transcription factors. Northern blot analysis of adult murine tissues revealed that themsimgene produces a single mRNA species of ∼4 kb expressed in a small number of tissues, with the highest levels in the kidneys and lower levels present in skeletal muscle, lung, testis, brain, and heart.In situhybridization experiments demonstrate thatmsimis also expressed in early fetal development in the central nervous system and in cartilage primordia. The characteristics of themsimgene are consistent with its putative function as a transcriptional regulator.