CHROMOSOMAL LOCALIZATION IN MOUSE AND HUMAN OF THE VASOACTIVE-INTESTINAL-PEPTIDE RECEPTOR-TYPE-2 GENE - A POSSIBLE CONTRIBUTOR TO THE HOLOPROSENCEPHALY-3 PHENOTYPE

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary ad enylate cyclase activating polypeptide (PACAP) have been shown to act on a wide range of tissue and cell types, both in the central nervous system and in the periphery. Two distinct receptors for VIP, the VIP r eceptor type 1 (VIPR1) and the VIP receptor type 2 (VIPR2), have recen tly been cloned, each of which binds PACAP and VIP with equal affinity . We report here the chromosomal mapping of the human and mouse VIPR2 genes by fluorescence in situ hybridization. The VIPR2 gene maps to th e human chromosomal region 7q36.3 and to the F2 region of mouse chromo some 12. Our localization of the human gene places it in the region wh ere the locus for the craniofacial defect holoprosencephaly type 3 (HP E3) maps. Further mapping experiments, carried out on cell lines deriv ed from patients with HPE or HPE microforms and associated 7q deletion s, have led us to redefine the distal extent of the HPE3 minimal criti cal region, originally characterized by Gurrieri ct al. (1993, Nature Genet. 3: 247-251.) The VIPR2 gene lies within this new HPE3 minimal c ritical region. Our results suggest that deletion of the VIPR2 gene is not the sole factor responsible for the HPE3 phenotype. However, it i s possible that monosomy at the VIPR2 locus may contribute to the phen otype observed in many cases of HPE3. (C) 1996 Academic Press, Inc.