Characterization of Adult Vestibular Organs in 11 CreER Mouse Lines

Abstract

Utricles are vestibular sense organs that encode linear head movements. They are composed of a sensory epithelium with type I and type II hair cells and supporting cells, sitting atop connective tissue, through which vestibular nerves project. We characterized utricular Cre expression in 11 murine CreER lines using the ROSA26^tdTomato reporter line and tamoxifen induction at 6 weeks of age. This characterization included Calbindin2^CreERT2, Fgfr3-iCreER^T2, GFAP-A-CreER™, GFAP-B-CreER™, GLAST-CreER^T2, Id2^CreERT2, Otoferlin^CreERT2, Parvalbumin^CreERT2, Prox1^CreERT2, Sox2^CreERT2, and Sox9-CreER^T2. Otoferlin^CreERT2 mice had inducible Cre activity specific to hair cells. GLAST-CreER^T2, Id2^CreERT2, and Sox9-CreER^T2 had inducible Cre activity specific to supporting cells. Sox2^CreERT2 had inducible Cre activity in supporting cells and most type II hair cells. Parvalbumin^CreERT2 mice had small numbers of labeled vestibular nerve afferents. Calbindin2^CreERT2 mice had labeling of most type II hair cells and some type I hair cells and supporting cells. Only rare (or no) tdTomato-positive cells were detected in utricles of Fgfr3-iCreER^T2, GFAP-A-CreER™, GFAP-B-CreER™, and Prox1^CreERT2 mice. No Cre leakiness (tdTomato expression in the absence of tamoxifen) was observed in Otoferlin^CreERT2 mice. A small degree of leakiness was seen in GLAST-CreER^T2, Id2^CreERT2, Sox2^CreERT2, and Sox9-CreER^T2 lines. Calbindin2^CreERT2 mice had similar tdTomato expression with or without tamoxifen, indicating lack of inducible control under the conditions tested. In conclusion, 5 lines-GLAST-CreER^T2, Id2^CreERT2, Otoferlin^CreERT2, Sox2^CreERT2, and Sox9-CreER^T2-showed cell-selective, inducible Cre activity with little leakiness, providing new genetic tools for researchers studying the vestibular periphery.

Keywords: CreER/loxP; FGFR3; GFAP; GLAST; Id2; Prox1; Sox2; Sox9; calbindin; fate-mapping; mouse genetics; otoferlin; parvalbumin; utricle.