Inducible Rbpms-CreERT2 mouse line for functional studies of genes in retinal ganglion cell physiology and disease
Retinal ganglion cells (RGCs) are the sole output neurons conveying visual stimuli from the retina to the brain and the dysfunction or loss of RGCs is the primary determinant of visual loss in traumatic and degenerative ocular conditions. Currently, there is a lack of RGC-specific Cre mouse lines that serve as invaluable tools for manipulating genes in RGCs and studying the genetic basis of RGC diseases. The RNA-binding protein with multiple splicing (RBPMS) is identified as the specific marker of all RGCs. Here, we report the generation and characterization of a knock-in mouse line in which a P2A-CreERT2 coding sequence is fused in-frame to the C-terminus of endogenous RBPMS, allowing the co-expression of RBPMS and CreERT2. The inducible Rbpms-CreERT2 mice exhibited a high recombination efficiency in activating the expression of tdTomato reporter gene in nearly all adult RGCs as well as in differentiated RGCs starting at E13.5. Additionally, heterozygous Rbpms-CreERT2 knock-in mice showed no detectable defect in the retinal structure, visual function and transcriptome. Altogether, our results demonstrated that the Rbpms-CreERT2/+ knock-in mouse can serve as a powerful and highly desired genetic tool for lineage tracing, genetic manipulation, retinal physiology study and ocular disease modeling in RGCs. Overall design: Whole retinas are usd for the sequencing and each pair of retinas from one mouse is taken as 1 sample. Among same litters, genotype with +/+ mice are taken as wild type control samples, Rbpms-CreERT2/+ mice are taken as the heterzygous knockout samples, Rbpms-CreERT2/CreERT2 mice are taken as the homozygous knockout samples.