A family of nonclassical class I MHC genes contributes to ultrasensitive chemodetection by mouse vomeronasal sensory neurons.
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 (ΔH2Mv 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 ΔH2Mv mice, whereas single V2r1b-expressing VSNs, which do not coexpress H2-Mv genes, show normal sensitivity to a peptide ligand in ΔH2Mv mice. Consistent with the greatly decreased VSN sensitivity, ΔH2Mv 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.
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.
Trese
T
Leinders-Zufall
Tomohiro
T
Ishii
Pablo
P
Chamero
Philipp
P
Hendrix
Livio
L
Oboti
Andreas
A
Schmid
Sarah
S
Kircher
Martina
M
Pyrski
Sachiko
S
Akiyoshi
Mona
M
Khan
Evelien
E
Vaes
Frank
F
Zufall
Peter
P
Mombaerts
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002628:Chemoreceptor Cells / Q000378:metabolism* / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D005805:Genes, MHC Class I / Q000235:genetics*; D018095:Germ-Line Mutation; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D012684:Sensory Thresholds; D012726:Sexual Behavior, Animal; D012903:Smell / Q000235:genetics*; D019147:Vomeronasal Organ / Q000166:cytology / Q000378:metabolism* / Q000502:physiology
D043562:Receptors, G-Protein-Coupled; D002118:Calcium
accessory olfactory system; chemodetection; chromosome engineering; major histocompatibility complex; pheromone; vomeronasal receptor