Figure 9.

Conditional knockout of Hcn1. A, Representative currents recorded from an Hcn1-floxed vestibular hair cell negative for GFP and Cre-recombinase. B, Currents recorded from an Hcn1-floxed hair cell positive for GFP and Cre-recombinase after transfection with an Ad-Cre-GFP. Note the complete lack of I_h, which resembles currents from Hcn1 deficient mice shown in Fig. 5B. C, I_h recorded from a wild-type GFP-positive hair cell transfected with Ad-Cre-GFP. D, Representative currents from a mouse with hair cell deletion of Hcn1 through expression of Foxg1 Cre-recombinase. Note the complete lack of I_h, similar to panel B and to Hcn1-deficient tissue. E, Mean maximum conductance from 11 Hcn1-floxed cells, 7 Hcn1-floxed cells infected with AdCre-GFP, 4 wild-type cells infected with AdCre-GFP, and 9 Hcn1-floxed cells expressing Cre under the Foxg1 promoter. Asterisks mark statistically significant differences (p<0.001) relative to Hcn1-floxed hair cells. F, Rotarod performance in 6 training trials of 20 conditional Hcn1 knockout mice (white bars), six mice positive for Foxg1-Cre (striped bars), and 24 Hcn1-floxed mice without Cre expression (gray bars). Mice were approximately 4 to 6 months old. Asterisks indicate statistically significant differences (*: p<0.05; **: p<0.005) between the Hcn1-floxed group and the Hcn1-floxed mice heterozygous for Foxg1-Cre. G, Performance of conditional Hcn1 knockouts on accelerating testing tasks was also significantly worse in two of the four trials than mice with floxed alleles but no Cre-recombinase. H, I, Peak-to-peak amplitude measurements of vestibular evoked potentials in three genotypes of mice. Amplitudes reported represented the difference in the first positive and first negative peak in the recorded waveform. Data were normalized to 0 dB SL which represented the threshold response. We noted a significant decrease in amplitude at 6 dB SL between the 14 Hcn1-floxed mice (white circles) and the 4 global Hcn1-deficient mice (gray triangles, H). There was also a significant decrease in amplitude at the 3 and 6 dB SL between 14 Hcn1-floxed mice (white circles) and the 10 Cre-positive Hcn1-floxed mice (gray squares, I).