CLONING, MESSENGER-RNA EXPRESSION, AND CHROMOSOMAL MAPPING OF MOUSE AND HUMAN PREPROCORTISTATIN

Cortistatin is a 14-residue putative neuropeptide with strong structur al similarity to somatostatin and is expressed predominantly in cortic al GABAergic interneurons of rats. Administration of cortistatin into the brain ventricles specifically enhances slow-wave sleep, presumably by antagonizing the effects of acetylcholine on cortical excitability . Here we report the identification of cDNAs corresponding to mouse an d human preprocortistatin and the mRNA distribution and gene mapping o f mouse cortistatin. Analysis of the nucleotide and predicted amino ac id sequences from rat and mouse reveals that the 14 C-terminal residue s of preprocortistatin, which make up the sequence that is most simila r to somatostatin, are conserved between species. Lack of conservation of other dibasic amino acid residues whose cleavage by prohormone con vertases would give rise to additional peptides suggests that cortista tin-14 is the only active peptide derived from the precursor. As in th e rat, mouse preprocortistatin mRNA is present in GABAergic interneuro ns in the cerebral cortex and hippocampus. The preprocortistatin gene maps to mouse chromosome 4, in a region showing conserved synteny with human 1p36. The human putative cortistatin peptide has an arginine fo r lysine substitution, compared to the rat and mouse products, and is N-terminally extended by 3 amino acids. (C) 1997 Academic Press.