Inducible CreERT2 Mouse Lines for Characterization of Retinal Bipolar Cell Subtypes.

Bipolar cells relay visual signals from photoreceptors to ganglion cells. In the mouse retina, 15 bipolar cell subtypes have been identified and are classified as ON or OFF bipolar cells based on their responses to light or as rod or cone bipolar cells based on their photoreceptor connectivity. Despite this diversity, the distinct structural and functional roles of bipolar cell subtypes in visual information processing remain poorly understood, largely due to lack of tools and models for their characterization. In this study, we generated inducible Cre mouse lines driven by the promoters of Vsx1, Lhx3, and Lhx4 and crossed them with ChR2EYFP reporter mice to trace lineage and characterize bipolar cell subtypes in postnatal and adult mouse retinas. Following tamoxifen induction in adult male and female mice, ChR2EYFP expression was detected in type 2, 6, and 7 bipolar cells in the Vsx1CreERT2 line; type 1b, 2, and 6 bipolar cells in the Lhx3CreERT2 line; and type 2, 3, 4, and 5 bipolar cells in the Lhx4CreERT2 line. In addition, Lhx4CreERT2 activity was observed in cone photoreceptor cells. ChR2EYFP expression was also detected in other ON and OFF cone bipolar cells, as well as rod bipolar cells, when tamoxifen induction was performed in the postnatal mice. These inducible Cre lines enable genetic manipulation in retinal bipolar cell subtypes at different developmental time points and serve as tools for elucidation of the mechanisms that control bipolar cell subtype development and function.