SummaryDuring development of the nervous system, neurons connect to one another in a precisely organized manner. Sensory systems provide a good example of this organization, whereby the composition of the outside world is represented in the brain by neuronal maps. Establishing correct patterns of neural circuitry is crucial, as inaccurate map formation can lead to severe disruptions in sensory processing. In rodents, olfactory stimuli modulate a wide variety of behaviors essential for survival. The formation of the olfactory glomerular map is dependent on molecular cues that guide olfactory receptor neuron axons to broad regions of the olfactory bulb and on cell adhesion molecules that promote axonal sorting into specific synaptic units in this structure. Here, we demonstrate that the cell adhesion molecule Amigo1 is expressed in a subpopulation of olfactory receptor neurons, and we investigate its role in the precise targeting of olfactory receptor neuron axons to the olfactory bulb using a genetic loss‐of‐function approach in mice. While ablation of Amigo1 did not lead to alterations in olfactory sensory neuron axonal targeting, our experiments revealed that the presence of a neomycin resistance selection cassette in the Amigo1 locus can lead to off‐target effects that are not due to loss of Amigo1 expression, including unexpected altered gene expression in olfactory receptor neurons and reduced glomerular size in the ventral region of the olfactory bulb. Our results demonstrate that insertion of a neomycin selection cassette into the mouse genome can have specific deleterious effects on the development of the olfactory system and highlight the importance of removing antibiotic resistance cassettes from genetic loss‐of‐function mouse models when studying olfactory system development.

中文翻译：

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在 Amigo1 基因座中插入新霉素选择盒会改变嗅觉上皮中的基因表达，导致嗅觉受体神经元发育的区域特异性缺陷

摘要在神经系统的发育过程中，神经元以一种精确组织的方式相互连接。感觉系统提供了这种组织的一个很好的例子，外部世界的组成在大脑中通过神经元图来表示。建立正确的神经回路模式至关重要，因为不准确的地图形成可能会导致感觉处理的严重破坏。在啮齿类动物中，嗅觉刺激调节多种对生存至关重要的行为。嗅觉肾小球图的形成依赖于引导嗅觉受体神经元轴突到达嗅球广泛区域的分子线索，以及促进轴突分类成该结构中特定突触单元的细胞粘附分子。在这里，我们证明细胞粘附分子 Amigo1 在嗅觉受体神经元亚群中表达，并且我们使用遗传功能丧失方法在小鼠中研究了其在嗅觉受体神经元轴突精确靶向嗅球中的作用。虽然 Amigo1 的消融并没有导致嗅觉感觉神经元轴突靶向的改变，但我们的实验表明，在嗅觉感觉神经元轴突靶向中存在新霉素抗性选择盒朋友1位点可能导致并非由于 Amigo1 表达缺失而导致的脱靶效应，包括嗅觉受体神经元中基因表达的意外改变以及嗅球腹侧区域肾小球尺寸的减小。我们的结果表明，在小鼠基因组中插入新霉素选择盒会对嗅觉系统的发育产生特定的有害影响，并强调在研究嗅觉系统发育时从遗传功能丧失小鼠模型中去除抗生素抗性盒的重要性。