MOLECULAR-CLONING OF A NOVEL MOUSE GENE WITH PREDOMINANT MUSCLE AND NEURAL EXPRESSION

Because numerous diseases affect the muscle and nervous systems, it is important to identify and characterize genes that may play functional roles in these tissues. Sequence analysis of a 106-kb region of human Chromosome (Chr) 19q13.2 revealed a novel gene with homology to the N euroendocrine-specific protein (NSP), and it has, therefore, been desi gnated NSP-like 1 (Nspl1). We isolated the mouse homolog of this gene and performed extensive expression analysis of both the mouse and huma n genes. The mouse Nspl1 gene is alternatively spliced to produce two major transcripts: a 2.1-kb mRNA that is expressed at highest levels i n the brain, and a 1.2-kb transcript that is primarily expressed in mu scle. The larger message contains 10 exons, whereas the smaller transc ript contains 7 exons. The last 6 exons, which are present in both tra nscripts, share significant amino acid sequence identity with the endo plasmic reticulum-bound portion of NSP. Mouse and human Nspl1/NSPL1 ge nes have expression patterns that are similar to that of the dystrophi n gene. In addition, the putative regulatory domains of Nspl1 appear s imilar in composition and distribution to the defined dystrophin regul atory sequences.