Figure 5. R306C mice recapitulate many RTT phenotypes.
(A–E) Behavioral tests were performed at 5 weeks of age to examine the R306C phenotype. At this age, WT (black, n = 18) and R306C Tg (blue, n = 17) mice are indistinguishable. Like the null mice (red, n = 14), R306C mice (green, n = 16) have increased anxiety, as measured by increased time spent in the dark in the light/dark assay (A), purposeful paw movement deficits as measured by their ability to build nests (B), motor dysfunction as measured by increased footslips per cm traveled in parallel rod footslip (C), and learning and memory deficits in contextual (D) and cued (E) fear conditioning. (F–J) Behavioral tests were performed on a new cohort of mice at 11 weeks of age, when most of the null mice have succumbed to disease, to examine any changes in the observed phenotypes. WT (n = 17) and R306C Tg (n = 15) mice remain indistinguishable at this age. R306C (n = 15) mice were hypoactive in the open field assay (F) and continue to exhibit increased anxiety as measured by decreased time spent in the center in the open field assay (G). Additionally, their motor dysfunction and learning and memory deficits have both worsened (H–J). The motor coordination of older R306C Tg mice was tested with a new cohort of 5 month old WT (n = 12) and R306C Tg (n = 11) mice subjected to rotarod (four trials a day for 4 days), and no difference was observed in their time spent on the rod (K). Data were analyzed by an ordinary one-way ANOVA followed by Tukey's multiple comparisons test. Results were plotted as the mean ± SEM. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.