Figure 8

Recovery of sensory transduction and balance function with Tm[Tmc2]. (A) Gfi1^cre recombination in Rosa26^tm(CAG-LSL-Tmc2-IRES-GFP) leads to GFP expression in hair cells of the utricle, here shown at P8 in Tmc1^Δ/ΔTmc2^Δ/+. Red: Actin-phalloidin; Green: GFP. Scale bar: 100 μm. (B) Sensory transduction is absent from GFP-negative cells but robust in GFP-positive cells in P3-P6 utricles of Gfi1^cre recombined mice under Tmc1^Δ/ΔTmc2^Δ/Δ background. (C) Expression of Tm[Tmc2] decreases circling behavior that is detected in absence of Tmc1 and Tmc2. Open field observations were performed for 5 min in 4 weeks old wild type C57BL6 (WT), Tmc1^Δ/ΔTmc2^Δ/Δ, and Tmc1^Δ/ΔTmc2^Δ/Δ expressing Tm[Tmc2] after Gfi1^cre recombination. Representative tracks over 2.5 min are shown. While Tmc1^Δ/ΔTmc2^Δ/Δ mice explore the entire field and perform repetitive full body rotations, Tm[Tmc2]; Tmc1^Δ/ΔTmc2^Δ/Δ mice demonstrate normal behavior similar to wild type controls. (D) Rotations were reduced in Tmc1^Δ/ΔTmc2^Δ/Δ expressing Tm[Tmc2]. The box plot illustrates the mean ± S.D. and median value for the number of rotations covered per minute for each genotype. (E) Rotational VOR responses to sinusoidal head rotation were recovered in Tmc1^Δ/ΔTmc2^Δ/Δ expressing Tm[Tmc2]. Gains and phases are plotted as functions of head rotation frequency for each group. Mean ± S.E.M for groups that have 3 or more mice. Pink lines with hollow circles in panel E represent individual animals due to sample size = 2. ***P < 0.001 (one way ANOVA).