DETERMINANTS OF CONNECTIVITY IN THE OLFACTORY SYSTEM

嗅觉受体由一个由1,000个或更多基因组成的家族编码， 小鼠 一个嗅觉神经元很可能只表达 这些基因。 表达给定受体的神经元分散在 嗅觉上皮的四个区域之一;生物学上 带状分布的意义仍然未知。神经元轴突 将给定的嗅觉受体项目表达给1800个中的两个 嗅球中的肾小球，造成了一个可怕的布线问题。 申办者之前的研究表明嗅觉受体 它本身在连接性，但它不能是唯一的决定因素， 指导过程。 在初步研究中，申请人着重于 M71和M72基因编码两种高度相关的受体， 都在同一上皮区表达。 M71和M72肾小球 被证明是不同的。 在这里，这些实验的延续 提出，旨在定义和描述两个决定因素， 嗅觉系统的连接：上皮区， 神经元的位置，以及嗅觉受体本身。 基因打靶 这项技术将被用来改造小鼠，使它们表达一种 多种敲入突变，主要在M71基因中。 的 实验与申办者先前的研究不同， 操作是用嗅觉受体基因进行的， 在同一个区域表达。

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.