A Family of Nonclassical Class I MHC Genes Contributes to Ultrasensitive Chemodetection by Mouse Vomeronasal Sensory Neurons
A Family of Nonclassical Class I MHC Genes Contributes to Ultrasensitive Chemodetection by Mouse Vomeronasal Sensory Neurons
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DOI：
10.1523/jneurosci.0186-14.2014
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发表时间：
2014-04-09
影响因子：
5.3
通讯作者：
Mombaerts, Peter
中科院分区：
文献类型：
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作者：
Leinders-Zufall, Trese;Ishii, Tomohiro;Mombaerts, Peter
小鼠犁鼻器（VNO）在化学通讯中起着关键作用。犁鼻感觉神经上皮由不同的犁鼻感觉神经元（VSNs）组成。一个子集的VSN，细胞体在基底层的基底部分，共表达Vmn 2 r G蛋白偶联受体基因与H2-Mv基因，一个家庭的9个非经典的I类主要组织相容性复合体基因。H2-Mv基因家族的体内生理作用在VSN中组合H2-Mv基因表达的发现之后的十多年中仍然是神秘的。在这里，我们已经采取了遗传学的方法，并删除了530 kb簇的H2-Mv基因在小鼠生殖细胞的染色体工程。纯合突变小鼠（Delta H2 Mv小鼠）是活的和可生育的。他们的VNO和副嗅球（AOB）没有重大的解剖缺陷。它们的VSN可以用化学刺激物（肽和蛋白质）刺激，达到与野生型小鼠的VSN相同的最大反应，但需要更高的浓度。这种生理表型在单细胞水平上展示，并且是细胞自主的：通常共表达H2-Mv基因的单个表达V2 rf 2的VSN在Delta H2 Mv小鼠中显示出对肽配体的敏感性降低，而不共表达H2-Mv基因的单个表达V2 r1 b的VSN在Delta H2 Mv小鼠中显示出对肽配体的正常敏感性。与VSN敏感性大大降低一致，Delta H2 Mv小鼠在攻击性和性行为方面表现出明显的缺陷。因此，H2-Mv基因对于生理反应的产生不是绝对必要的，但是对于VSN的子集的超灵敏化学检测是必需的。
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.