CD20 is a mammalian odorant receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators

The mammalian olfactory system detects and discriminates between millions of odorants to elicit appropriate behavioral responses. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, how specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains poorly understood. Here, we show that the 4-transmembrane protein CD20, also known as MS4A1, is expressed in a previously uncharacterized subpopulation of olfactory sensory neurons in the main olfactory epithelium of the murine nasal cavity and functions as a mammalian odorant receptor that recognizes compounds produced by mouse predators. While wildtype mice avoid these predator odorants, mice genetically deleted of CD20 do not appropriately respond. Together, this work reveals a novel CD20-mediated odor-sensing mechanism in the mammalian olfactory system that triggers innate behaviors critical for organismal survival. To characterize role of the Ms4a genes in the mouse olfactory system, we generated the Ms4a6c knockout and whole Ms4a cluster knockout mice. To validate the gene expression of these knockout mice, we generate the cDNA library from the olfactory epithelium from wild-type, Ms4a6c KO, and whole Ms4a cluster knockout mice (3 biological replicates per genotype.哺乳动物嗅觉系统可感知并区分数百万种气味分子，以触发适配的行为反应。尽管学界已对嗅觉感觉神经元如何识别气味分子并传递其存在信号已有较多研究，但针对特定先天、非习得行为如何响应行为学相关气味而被触发的机制，目前仍知之甚少。本研究发现，四次跨膜蛋白CD20（MS4A1）在小鼠鼻腔主嗅觉上皮中一类此前未被表征的嗅觉感觉神经元亚群中表达，并作为哺乳动物气味受体识别小鼠捕食者产生的化合物。野生型小鼠会规避这类捕食者气味化合物，而CD20基因敲除小鼠则无法做出恰当响应。综上，本研究揭示了哺乳动物嗅觉系统中一种由CD20介导的新型气味感知机制，该机制可触发对生物体生存至关重要的先天行为。为表征Ms4a家族基因在小鼠嗅觉系统中的功能，我们构建了Ms4a6c基因敲除小鼠与全Ms4a基因簇敲除小鼠。为验证这些敲除小鼠的基因表达情况，我们分别从野生型、Ms4a6c基因敲除型与全Ms4a基因簇敲除型小鼠的嗅觉上皮中提取样本，构建了互补DNA（cDNA）文库（每种基因型设置3个生物学重复）。