Nerves of the peripheral nervous system contain two classes of Schwann cells: myelinating Schwann cells that ensheath large caliber axons and generate the myelin sheath, and Remak Schwann cells that surround smaller axons and do not myelinate. While tools exist for genetic targeting of Schwann cell precursors and myelinating Schwann cells, such reagents have been challenging to generate specifically for the Remak population, in part because many of the genes that mark this population in maturity are also robustly expressed in Schwann cell precursors. To circumvent this challenge, we utilized BAC transgenesis to generate a mouse line expressing a tamoxifen-inducible Cre under the control of a Remak-expressed gene promoter (Egr1). However, as Egr1 is also an activity dependent gene expressed by some neurons, we flanked this Cre by flippase (Flpe) recognition sites, and coinjected a BAC expressing Flpe under control of a pan-neuronal Snap25 promoter to excise the Cre transgene from these neuronal cells. Genotyping and inheritance demonstrate that the two BACs co-integrated into a single locus, facilitating maintenance of the line. Anatomical studies following a cross to a reporter line show sparse tamoxifen-dependent recombination in Remak Schwann cells within the mature sciatic nerve. However, depletion of neuronal Cre activity by Flpe is partial, with some neurons and astrocytes also showing evidence of Cre reporter activity in the central nervous system. Thus, this mouse line will be useful in mosaic loss-of-function studies, lineage tracing studies following injury, live cell imaging studies, or other experiments benefiting from sparse labeling.

中文翻译：

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一种可诱导的 Cre 小鼠系，可稀疏地靶向神经系统细胞，包括 Remak Schwann 细胞。

周围神经系统的神经包含两类雪旺细胞：包裹大口径轴突并产生髓鞘的髓鞘化雪旺细胞，以及围绕较小轴突但不形成髓鞘的 Remak 雪旺细胞。虽然存在用于雪旺细胞前体和髓鞘形成的雪旺细胞的基因靶向工具，但此类试剂一直难以专门为 Remak 群体生成，部分原因是许多标记该群体成熟的基因也在雪旺细胞前体中强烈表达。为了规避这一挑战，我们利用 BAC 转基因在 Remak 表达基因启动子 (Egr1) 的控制下生成表达他莫昔芬诱导型 Cre 的小鼠品系。然而，由于 Egr1 也是一些神经元表达的活性依赖基因，我们在这个 Cre 的两侧设置了翻转酶 (Flpe) 识别位点，并在泛神经元 Snap25 启动子的控制下共同注入了表达 Flpe 的 BAC，以从这些神经元细胞中切除 Cre 转基因。基因分型和遗传表明，两个 BAC 共同整合到一个基因座中，促进了品系的维护。与报告线交叉后的解剖学研究表明，成熟坐骨神经内的 Remak Schwann 细胞中存在稀疏的他莫昔芬依赖性重组。然而，Flpe 对神经元 Cre 活性的消耗是部分的，一些神经元和星形胶质细胞也显示出中枢神经系统中 Cre 报告基因活动的证据。因此，该小鼠品系将可用于马赛克功能丧失研究、受伤后的谱系追踪研究、活细胞成像研究或其他受益于稀疏标记的实验。