Journal
JOURNAL OF NEUROSCIENCE
Volume 34, Issue 15, Pages 5121-5133Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0186-14.2014
Keywords
accessory olfactory system; chemodetection; chromosome engineering; major histocompatibility complex; pheromone vomeronasal receptor
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Funding
- National Institutes of Health [DA011322, DA021696, DA014277, DA036385, DA015916]
- Lilly Foundation
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The mouse vomeronasal organ (VNO) has a pivotal role in chemical communication. The vomeronasal sensory neuroepithelium consists of distinct populations of vomeronasal sensory neurons (VSNs). A subset of VSNs, with cell bodies in the basal part of the basal layer, coexpress Vmn2r G-protein-coupled receptor genes with H2-Mv genes, a family of nine nonclassical class I major histocompatibility complex genes. The in vivo, physiological roles of the H2-Mv gene family remain mysterious more than a decade after the discovery of combinatorial H2-Mv gene expression in VSNs. Here, we have taken a genetic approach and have deleted the 530 kb cluster of H2-Mv genes in the mouse germline by chromosome engineering. Homozygous mutant mice (Delta H2Mv mice) are viable and fertile. There are no major anatomical defects in their VNO and accessory olfactory bulb (AOB). Their VSNs can be stimulated with chemostimuli (peptides and proteins) to the same maximum responses as VSNs of wild-type mice, but require much higher concentrations. This physiological phenotype is displayed at the single-cell level and is cell autonomous: single V2rf2-expressing VSNs, which normally coexpress H2-Mv genes, display a decreased sensitivity to a peptide ligand in Delta H2Mv mice, whereas single V2r1b-expressing VSNs, which do not coexpress H2-Mv genes, show normal sensitivity to a peptide ligand in Delta H2Mv mice. Consistent with the greatly decreased VSN sensitivity, Delta H2Mv mice display pronounced deficits in aggressive and sexual behaviors. Thus, H2-Mvgenes are not absolutely essential for the generation of physiological responses, but are required for ultrasensitive chemodetection by a subset of VSNs.
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