An inducible Cre mouse line to sparsely target nervous system cells, including Remak Schwann cells

Abstract

Nerves of the peripheral nervous system contain two classes of Schwann cells- myelinating Schwann cells that ensheath large caliber axons in myelin, and Remak Schwann cells that surround smaller axons and do not myelinate. While tools exist for genetic targeting of myelinating Schwann cells, such reagents have been challenging to generate for the Remak population in part because many of the genes that mark this population in maturity are also robustly expressed in progenitors of all Schwann cells. 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 target 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, and live cell imaging studies or other experiment benefiting from sparse labeling.