1. The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
2. Department of Anatomy and Neurobiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
3. Monell Chemical Senses Center, 3500 Market Street, Philadelphia, Pennsylvania 19104, USA
4. Present address: Department of Zoology and Animal Biology, Faculty of Sciences, University of Geneva, CH-1211 Geneva 4, Switzerland.

Correspondence to: Peter Mombaerts¹ Correspondence and requests for materials should be addressed to P.M. (e-mail: Email: peter@rockefeller.edu).

Abstract

The mammalian vomeronasal organ (VNO), a part of the olfactory system, detects pheromones—chemical signals that modulate social and reproductive behaviours^{1, 2}. But the molecular receptors in the VNO that detect these chemosensory stimuli remain undefined. Candidate pheromone receptors are encoded by two distinct and complex superfamilies of genes, V1r and V2r (refs 3 and 4), which code for receptors with seven transmembrane domains. These genes are selectively expressed in sensory neurons of the VNO. However, there is at present no functional evidence for a role of these genes in pheromone responses. Here, using chromosome engineering technology⁵, we delete in the germ line of mice a 600-kilobase genomic region that contains a cluster of 16 intact V1r genes⁶. These genes comprise two of the 12 described V1r gene families⁷, and represent 12% of the V1r repertoire. The mutant mice display deficits in a subset of VNO-dependent behaviours: the expression of male sexual behaviour and maternal aggression is substantially altered. Electrophysiologically, the epithelium of the VNO of such mice does not respond detectably to specific pheromonal ligands. The behavioural impairment and chemosensory deficit support a role of V1r receptors as pheromone receptors.