Figure 4.

Expression of the FlexCln3 allele in neurons alone does not prevent autofluorescent lipofuscin accumulation in cortical neurons

(A–C) There is little autofluorescent lipofuscin accumulation (green) in wild-type cortical neurons (red) (blue DAPI) compared with (D–F) Cln3^Δ78/Δ78 cortical neurons in 12-month-old animals. (G–I) Zp3-Cre-induced expression of the FlexCln3 allele in all cell types prevents autofluorescent lipofuscin accumulation in both neuronal and non-neuronal cells. (J–L) FlexCln3 expression in neurons (Syn1-Cre) did not prevent storage accumulation in neurons (arrowheads) or non-neuronal cells (arrows). (M) Quantification of autofluorescence in neurons confirms storage accumulation in NeuN-positive cells after neuronal rescue. Three mice per group were analyzed with three images per mouse. Each image was fragmented for NeuN immunostaining, and autofluorescence was quantified in 238 or more NeuN-positive cells per group. Data represent mean gray value for each cell. Statistical analysis was performed with repeated measures one-way ANOVA followed by Sidak’s multiple comparisons test. ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001.