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嗅觉受体基因选择和嗅受体基因 SR1 缺失突变小鼠的轴突布线

Odorant receptor gene choice and axonal wiring in mice with deletion mutations in the odorant receptor gene SR1.

机构信息

The Rockefeller University, New York, NY 10065, USA; Bogazici University, Department of Molecular Biology and Genetics, 34342 Bebek, Istanbul, Turkey.

出版信息

Mol Cell Neurosci. 2013 Sep;56:212-24. doi: 10.1016/j.mcn.2013.05.002. Epub 2013 May 18.

DOI:10.1016/j.mcn.2013.05.002
PMID:23688909
Abstract

In the mouse, a mature olfactory sensory neuron (OSN) of the main olfactory epithelium (MOE) expresses one allele of one of the 1200 odorant receptor (OR) genes in the genome. The mechanisms that underlie the one receptor-one neuron rule remain poorly understood. A popular experimental paradigm for OR gene choice is to delete an OR coding region by gene targeting or in a transgene. Here we have applied this ∆OR paradigm to SR1, also known as MOR256-3 or Olfr124. This gene is expressed in OSNs of the MOE, and in ~50% of the OSNs of the septal organ. In heterozygous ∆SR1 mice, we observe an unprecedented biallelic expression rate of 30% at the SR1 locus. In homozygous ∆SR1 mice, we find a significant increase in the number of septal organ OSNs that undergo apoptosis. As a population, ∆SR1 OSNs project their axons to 81-85 glomeruli in each half of the OB, and coexpress at least 77 OR genes as evaluated by single-cell molecular analysis. There are no obvious or simple rules for the set of OR genes that are coexpressed with the ∆SR1 allele. The frequencies of coexpression are different for ∆SR1 OSNs in the septal organ compared to those in the MOE. We propose that there are as many as five scenarios for the fate of individual ∆SR1 OSNs.

摘要

在老鼠中,成熟的嗅上皮感觉神经元(OSN)表达基因组中 1200 个气味受体(OR)基因之一的一个等位基因。支持一个受体-一个神经元规则的机制仍未被很好地理解。一个流行的 OR 基因选择实验范例是通过基因靶向或转基因来删除 OR 编码区。在这里,我们将这种 ∆OR 范例应用于 SR1,也称为 MOR256-3 或 Olfr124。该基因在嗅上皮 OSN 中表达,在隔区器官的大约 50%的 OSN 中表达。在杂合子 ∆SR1 小鼠中,我们观察到 SR1 基因座的前所未有的双等位基因表达率为 30%。在纯合子 ∆SR1 小鼠中,我们发现凋亡的隔区器官 OSN 数量显著增加。作为一个群体,∆SR1 OSN 将其轴突投射到每一半 OB 中的 81-85 个肾小球中,并且通过单细胞分子分析评估至少共表达 77 个 OR 基因。与 ∆SR1 等位基因共表达的 OR 基因集没有明显或简单的规则。与 MOE 相比,∆SR1 OSN 在隔区器官中的共表达频率不同。我们提出,个别 ∆SR1 OSN 的命运可能有多达五种情况。

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