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J Neurosci

Title:		A family of nonclassical class I MHC genes contributes to ultrasensitive chemodetection by mouse vomeronasal sensory neurons
Author(s):		Leinders-Zufall T; Ishii T; Chamero P; Hendrix P; Oboti L; Schmid A; Kircher S; Pyrski M; Akiyoshi S; Khan M; Vaes E; Zufall F; Mombaerts P;
Address:		"Department of Physiology, University of Saarland School of Medicine, 66421 Homburg, Germany, Max Planck Research Unit for Neurogenetics, 60438 Frankfurt, Germany, and Department of Cell Biology and Center for Brain Integration Research, Tokyo Medical and Dental University, Graduate School of Medical and Dental Science, Bunkyo-ku, Tokyo 113-8510, Japan"
Journal Title:		J Neurosci
Year:		2014
Volume:		34
Issue:		15
Page Number:		5121 - 5133
DOI:		10.1523/JNEUROSCI.0186-14.2014
ISSN/ISBN:		1529-2401 (Electronic) 0270-6474 (Print) 0270-6474 (Linking)
Abstract:		"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 (DeltaH2Mv 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 DeltaH2Mv mice, whereas single V2r1b-expressing VSNs, which do not coexpress H2-Mv genes, show normal sensitivity to a peptide ligand in DeltaH2Mv mice. Consistent with the greatly decreased VSN sensitivity, DeltaH2Mv mice display pronounced deficits in aggressive and sexual behaviors. Thus, H2-Mv genes are not absolutely essential for the generation of physiological responses, but are required for ultrasensitive chemodetection by a subset of VSNs"
Keywords:		"Animals Calcium/metabolism Cell Line Chemoreceptor Cells/*metabolism/physiology Female Gene Deletion Genes, MHC Class I/*genetics Germ-Line Mutation Homozygote Male Mice Mice, Inbred C57BL Phenotype Receptors, G-Protein-Coupled/genetics/metabolism Sensory;"
Notes:		"MedlineLeinders-Zufall, Trese Ishii, Tomohiro Chamero, Pablo Hendrix, Philipp Oboti, Livio Schmid, Andreas Kircher, Sarah Pyrski, Martina Akiyoshi, Sachiko Khan, Mona Vaes, Evelien Zufall, Frank Mombaerts, Peter eng Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2014/04/11 J Neurosci. 2014 Apr 9; 34(15):5121-33. doi: 10.1523/JNEUROSCI.0186-14.2014"