Deficient pheromone responses in mice lacking a cluster of vomeronasal receptor genes

• Published in: Nature (London) Vol. 419; no. 6902; pp. 70 - 74
• Main Authors: Mombaerts, Peter, Del Punta, Karina, Leinders-Zufall, Trese, Rodriguez, Ivan, Jukam, David, Wysocki, Charles J, Ogawa, Sonoko, Zufall, Frank
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 05-09-2002; Nature Publishing Group
• Subjects: Aggression - drug effects; Animal behavior; Animals; Biological and medical sciences; Body Weight - drug effects; Chemicals; Depression; Electrophysiology; Estrous Cycle - drug effects; Evolution, Molecular; Female; Fundamental and applied biological sciences. Psychology; Gene Deletion; Genes; Ligands; Male; Mammals; Mice; Mice, Knockout; Motor Activity - drug effects; Multigene Family - genetics; Olfactory system and olfaction. Gustatory system and gustation; Pheromones - metabolism; Pheromones - pharmacology; Phylogeny; Receptors, Odorant - deficiency; Receptors, Odorant - genetics; Receptors, Odorant - metabolism; Rodents; Sensory perception; Sexual behavior; Sexual Behavior, Animal - drug effects; Smell - drug effects; Vertebrates: nervous system and sense organs; Vomeronasal Organ - cytology; Vomeronasal Organ - drug effects; Vomeronasal Organ - metabolism; Vertebrata; Mammalia; Gene; Mouse; Rodentia; Pheromone; Mutation; Vomeronasal organ; Olfactory system; Biological receptor
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature00955

The mammalian vomeronasal organ (VNO), a part of the olfactory system, detects pheromones-chemical signals that modulate social and reproductive behaviours. 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 technology, we delete in the germ line of mice a ∼600-kilobase genomic region that contains a cluster of 16 intact V1r genes. These genes comprise two of the 12 described V1r gene families, 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.