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

Karina Del Punta, Trese Leinders-Zufall, Ivan Rodriguez, David Jukam, Charles J. Wysocki, Sonoko Ogawa, Frank Zufall and Peter Mombaerts ()
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Karina Del Punta: The Rockefeller University
Trese Leinders-Zufall: University of Maryland School of Medicine
Ivan Rodriguez: The Rockefeller University
David Jukam: The Rockefeller University
Charles J. Wysocki: Monell Chemical Senses Center
Sonoko Ogawa: The Rockefeller University
Frank Zufall: University of Maryland School of Medicine
Peter Mombaerts: The Rockefeller University

Nature, 2002, vol. 419, issue 6902, 70-74

Abstract: Abstract The mammalian vomeronasal organ (VNO), a part of the olfactory system, detects pheromones—chemical signals that modulate social and reproductive behaviours1,2. 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.

Date: 2002
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DOI: 10.1038/nature00955

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