Coordinated coexpression of two vomeronasal receptor V2R genes per neuron in the mouse
Coordinated coexpression of two vomeronasal receptor V2R genes per neuron in the mouse
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DOI：
10.1016/j.mcn.2010.11.002
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发表时间：
2011-02-01
影响因子：
3.5
通讯作者：
Mombaerts, Peter
中科院分区：
文献类型：
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作者：
Ishii, Tomohiro;Mombaerts, Peter
小鼠犁鼻器（VNO）感觉神经元对化学感觉刺激的检测主要由7个跨膜受体介导，这些受体由V1R和V2R两大基因库编码。小鼠基因组包含122个完整的V2R基因，按序列同源性可分为4个家族：A、b、D家族（115个基因）和C家族（7个基因）。VNO上皮基底层的Vomeronasal感觉神经元（VSNs）以非随机组合共表达两个V2R基因：一个家族- abd V2R基因与一个家族- c V2R基因，如Vmn2r1（29%的基底VSNs）或Vmn2r2（52%）。这种协调的共表达可能有助于VSNs高度特化的感觉反应谱，例如abd家族与c家族V2R的异源二聚化。调控基底VSN中两个V2R基因协同表达的机制尚不清楚。在可能的模型中有顺序的和依赖的表达模型；一个随机组合表达的模型，然后选择合适组合的VSNs细胞；另一个基因家族如编码转录因子的基因直接协调基因表达的模型。在这里，我们描述了在abd V2R基因V2rf2家族中具有靶向突变的两种新型小鼠品系，它们开始为这个问题提供见解。我们观察到，绝大多数表达完整V2rf2共表达Vmn2r1的VSNs表达免疫反应性，并且Vmn2r1共表达的百分比从3周到10周增加。在建立了V2rf2与Vmn2r1的紧密共表达后，我们想知道当V2rf2的编码序列被删除时，这种紧密共表达是否保持。我们发现，在V2rf2编码序列中表达一个有目标缺失的位点（可能是零突变）的vsn数量与表达完整V2rf2的vsn数量相似。但其中25%的vsn共表达另一个家族abd V2R，这与V2rf2突变位点缺乏负反馈是一致的。有趣的是，9.5%表达V2rf2靶向缺失的VSNs现在共表达Vmn2r2。最后，在出生后野生型小鼠的VNO上皮边缘区域，即未成熟vsn集中的区域，abd家族V2R基因的RNA多于c家族基因的RNA。我们的结果与基础VSN中两个V2R基因协调共表达的顺序和依赖模型最为一致。(C) 2010爱思唯尔公司版权所有。
The detection of chemosensory stimuli by the sensory neurons of the mouse vomeronasal organ (VNO) is mainly mediated by seven-transmembrane receptors that are encoded by two large gene repertoires, V1R and V2R. The mouse genome contains 122 intact V2R genes, which can be grouped in four families by sequence homology: families A, B. and D (115 genes), and family C (7 genes). Vomeronasal sensory neurons (VSNs) in the basal layer of the VNO epithelium coexpress two V2R genes in non-random combinations: one family-ABD V2R gene together with one family-C V2R gene, such as Vmn2r1 (29% of basal VSNs) or Vmn2r2 (52%). This coordinated coexpression may contribute to the highly specialized sensory response profiles of VSNs, for instance by heterodimerization of a family-ABD with a family-C V2R. The mechanisms that regulate this coordinated cooexpression of two V2R genes per basal VSN are not understood. Among possible models are a sequential and dependent model of expression; a model of random combinations of expression followed by cellular selection of VSNs with appropriate combinations; and a model of direct coordination of gene expression by another gene family such as genes encoding transcription factors. Here, we describe two novel mouse strains with targeted mutations in the family-ABD V2R gene V2rf2 that begin to provide insight into this problem. We observe that the great majority of VSNs that express intact V2rf2 coexpress Vmn2r1 immunoreactivity, and that the percentage of Vmn2r1 coexpression increases from 3 to 10 wk. Having established this tight coexpression of V2rf2 with Vmn2r1, we then asked if it is maintained when the coding sequence of V2rf2 is deleted. We find that the number of VSNs expressing a locus with a targeted deletion in the coding sequence of V2rf2 that is likely a null mutation, is similar to the number of VSNs that express intact V2rf2. But 25% of these VSNs coexpress another family-ABD V2R, which is consistent with the absence of negative feedback from the mutated V2rf2 locus. Interestingly, 9.5% of VSNs expressing the targeted deletion of V2rf2 now coexpress Vmn2r2. Finally, the marginal region of the VNO epithelium, where immature VSNs are concentrated, has more RNA of family-ABD V2R genes than of family-C genes in postnatal wild-type mice. Our results are most consistent with the sequential and dependent model for the coordinated coexpression of two V2R genes per basal VSN. (C) 2010 Elsevier Inc. All rights reserved.