DETERMINANTS OF CONNECTIVITY IN THE OLFACTORY SYSTEM

嗅觉受体是由1,000个或更多基因家族编码的 老鼠。嗅觉感觉神经元很可能只表达一种 这些基因。表达特定受体的神经元散布在 嗅觉上皮中的四个区域之一； 这种纬向格局的意义尚不清楚。神经元的轴突 向1800人中的两人表达给定的嗅觉感受器项目 嗅球中的肾小球，构成了一个可怕的布线问题。 赞助商之前的研究表明，嗅觉受体 在连通性方面，但它不能是 指导过程。在初步研究中，申请人将重点放在 M71和M72基因，它们编码两个高度相关的受体 均在同一上皮区表达。M71和M72肾小球 被证明是截然不同的。在这里，这些实验的继续 旨在定义和描述以下两个决定因素 嗅觉系统中的连通性：嗅觉系统的上皮区 神经元和嗅觉感受器本身都被定位了。基因打靶 技术将被用来改造老鼠，使它们表达一种 多种敲入突变，主要发生在M71基因。这个 实验与赞助商之前的研究不同之处在于 操纵是通过嗅觉受体基因进行的，这些基因 在同一区域表达。

Olfactory receptors are encoded by a family of 1,000 or more genes in mice. An olfactory sensory neuron expresses most likely only one of these genes. Neurons expressing a given receptor are scattered within one of four zones in the olfactory epithelium; the biological significance of the zonal pattern remains unknown. Axons of neurons expressing a given olfactory receptor project to two out of 1,800 glomeruli in the olfactory bulb, posing a formidable wiring problem. Previous studies by the sponsor have implicated the olfactory receptor itself in connectivity, but it cannot be the only determinant in the guidance process. In preliminary studies the applicant has focused on the M71 and M72 genes, which encode two highly related receptors that are expressed in the same epithelial zone. The M71 and M72 glomeruli were shown to be distinct. Here, a continuation of these experiments is proposed that seeks to define and describe two determinants of connectivity in the olfactory system: the epithelial zone in which the neurons are located, and the olfactory receptor itself. Gene targeting technology will be used to engineer mice such that they express a variety of knock-in mutations, mostly in the M71 gene. The experiments differ from previous studies by the sponsor in that genetic manipulation is carried out with olfactory receptor genes that are expressed in the same zone.