The main olfactory epithelium (MOE) of an adult mouse harbors a few million mature olfactory sensory neurons (OSNs), which are traditionally defined as mature by their expression of the olfactory marker protein (OMP). Mature OSNs differentiate in situ from stem cells at the base of the MOE. The consensus view is that mature OSNs have a defined lifespan and then undergo programmed cell death, and that the adult MOE maintains homeostasis by generating new mature OSNs from stem cells. But there is also evidence for mature OSNs that are long-lived. Thus far modern genetic tools have not been applied to quantify survival of a population of OSNs that are mature at a given point in time. Here, a genetic strategy was developed to label irreversibly OMP-expressing OSNs in mice. A gene-targeted OMP-CreERT2 strain was generated in which mature OSNs express an enzymatically inactive version of the Cre recombinase. The fusion protein CreERT2 becomes transiently active when exposed to tamoxifen, and in the presence of a Cre reporter in the genome such as tdRFP, CreERT2-expressing cells become irreversibly labeled. A cohort of mice was generated with the same day of birth by in vitro fertilization and embryo transfer, and injected tamoxifen in their mothers at E18.5 of gestation. I counted RFP immunoreactive cells in the MOE and vomeronasal organ of 36 tamoxifen-exposed OMP-CreERT2 × tdRFP mice from 7 age groups: postnatal day (PD)1.5, PD3.5, PD6.5, 3 weeks, 9 weeks, 6 months, and 12 months. Approximately 7.8% of perinatally labeled cells remain at 12 months, confirming that some mature OSNs are indeed long-lived. The survival curve of the population of perinatally labeled MOE cells can be modeled with a mean half-life of 26 days for the population as a whole, excluding the long-lived cells.

成年小鼠的主要嗅觉上皮（MOE）带有数百万个成熟的嗅觉感觉神经元（OSN），传统上通过嗅觉标记蛋白（OMP）的表达将它们定义为成熟的。成熟的OSN在MOE的基部从干细胞中原位分化。共识认为，成熟的OSN具有确定的寿命，然后经历程序性的细胞死亡，而成年的MOE通过从干细胞生成新的成熟OSN来维持体内平衡。但是也有证据表明，成熟的OSN具有很长的使用寿命。迄今为止，尚未使用现代遗传工具来量化在给定时间点成熟的OSN种群的生存。在这里，开发了一种遗传策略来标记小鼠中不可逆地表达OMP的OSN。生成了基因靶向的OMP-CreERT2菌株，其中成熟的OSNs表达了Cre重组酶的酶促失活形式。当暴露于他莫昔芬时，融合蛋白CreERT2变为瞬时活性，并且在基因组中存在Cre报告基因（如tdRFP）时，表达CreERT2的细胞被不可逆地标记。通过体外受精和胚胎移植，在出生的同一天产生了一组小鼠，并在妊娠E18.5时向其母亲体内注射了他莫昔芬。我对来自7个年龄组的36例他莫昔芬暴露的OMP-CreERT2×tdRFP小鼠的MOE和犁鼻器官中的RFP免疫反应细胞进行了计数，这些小鼠来自以下7个年龄组：出生后（PD）1.5，PD3.5，PD6.5、3周，9周，6个月，以及12个月。围产期标记的细胞约有7.8％保留在12个月，这证实了某些成熟的OSN确实是长寿的。