CLONING AND CHARACTERIZATION OF A NOVEL HUMAN CLATHRIN HEAVY-CHAIN GENE (CLTCL)

An exon representing a novel clathrin heavy chain gene (CLTCL) was iso lated during gene identification studies and transcription mapping of human chromosome 22. Isolation and sequencing of cDNA clones correspon ding to this exon revealed extensive similarity of the predicted amino acid sequence of this gene product to those of clathrin heavy chain g enes of other species. Northern blot analysis has revealed an apparent developmental expression pattern of an approximately 6-kb mRNA. The g ene appears to be expressed ubiquitously in the limited number of feta l tissues that were tested, but is selectively expressed in certain ad ult tissues, particularly in skeletal muscle. In addition, alternative splicing of an exon was observed near the carboxyl terminus of the pr edicted gene product. Its location overlaps the domain putatively invo lved in clathrin light chain binding and is adjacent to the heavy chai n self-assembly (or trimerization) region, suggesting that alternative splicing may be involved in regulating one or both of these interacti ons. The expression pattern of this gene, in addition to its potential role in receptor-mediated endocytosis and signal transduction, sugges ts that it may be important in some developmental processes, The locat ion of CLTCL on human chromosome 22 near the region commonly deleted i n DiGeorge and other apparent haploinsufficiency syndromes warrants fu rther investigation into its relationship with these developmental dis orders. (C) 1996 Academic Press, Inc.