Figure 4. Aged Ttbk2^c.mut animals lose Purkinje cells.

(A) Representative images showing folia of 4-month-old Ttbk2^c.mut (top) and 6-month-old Ttbk2^c.mut animals (bottom) with respective littermate Controls. Cerebellum tissue is stained for Calbindin to show PC. 6-month-old Ttbk2^c.mut have large stretches of folia missing Calbindin+ PC soma compared to 4-month-old Ttbk2^c.mut. Scale bar 50 μm. (B) Quantification of the loss of PC soma along 500 μm stretch of the primary fissure (n = 36 measurements across three animals. p<0.0001 by student’s unpaired t-test, error bars indicate SEM). (C) Quantification of location of PC gaps in Ttbk2^c.mut animals. PC gaps are present throughout folia I-IX in Ttbk2^c.mut animals but are not seen in Controls. A threshhold of more than two cell spaces was used to define a PC gap. 10 cerebellar slices were quantified, n = 3 animals.

Figure 4—figure supplement 1. PC gaps are present throughout most cerebellar folia in 6-month -old Ttbk2^c.mut animals.

(A) Representative images of Calbindin staining (red) throughout the cerebellum of 6-month-old Control and Ttbk2^c.mut animals. Arrowheads denote gaps in folia present in Ttbk2^c.mut animals. Scale bar = 200 μm. Inset shows typical PC gap at higher magnification.

Figure 4—figure supplement 2. Neurons in the cortex of 6-month-old Ttbk2^c.mut animals have some Tau accumulation.

(A) Representative images of neurons in the cortex of 6-month-old Control, 4-month-old Ttbk2^c.mut, 6-month-old Ttbk2^c.mut and 55-week-old JNPL3(P301L) (B) animals showing AT8 phosphorylated Tau in red. JNPL3(P301L) mice express mutated Tau and were used as a positive Control for Tau accumulation. We did not detect any phosphorylated Tau in 4-month-old Ttbk2^c.mut animals; however, some neurons in the cortex of 6-month-old Ttbk2^c.mut have mild accumulation of phosphorylated Tau. Scale bar = 10 μm.