Fig. 3: Pharmacogenetic ablation of Split^Cre-Aβ-LTMRs.

A Illustration showing the intersectional genetic strategy to generate Split^Cre-Aβ TauDTR mice and the protocol timeline. RNAscope of tdTomato with lumbar DRG sections showing tdTomato+ DRG neurons in vehicle (B) and DTA-treated (C) mice. D Quantification of the tdTomato⁺ neurons per DRG showed a significant decrease with DTA treatment, p < 0.0001. The data were normalized to the average number of tdTomato⁺ DRG neurons/section of control mice. 3–4 sections/mouse, n = 3 mice in both groups. E, F Images showing tdTomato⁺ central terminals in the dorsal horn of the lumbar spinal cord of vehicle or DTA treated mice. Dotted white area indicates laminae III-V. G Quantification of the mean tdTomato⁺ fluorescence intensity in laminae III-V showed a significant decrease with DTA treatment, p = 0.0079. The data were normalized to the average mean intensity of Tdt⁺ central terminals of control mice. 6-8 sections per mouse, n = 5 mice. H, I Images showing tdTomato+ innervation in the Meissner’s corpuscles of vehicle or DTA-treated mice. White arrowheads indicate Meissner’s corpuscles innervated with tdTom+ fibers, and red arrow points to the Meissner’s corpuscle without tdTomato+. J Quantification of the number of tdTomato+ fibers innervating Meissner’s corpuscles per footpad section showed a significant decrease with DTA treatment, p = 0.0022. The data were normalized to the average number of tdTomato+ fibers innervating dermal papillae of control mice. 5–6 sections per mouse, n = 6 mice. K, L RNAscope of tdTomato, Ret, and Ntrk2⁺ with lumbar DRG sections of vehicle or DTA-treated mice. M, N RNAscope of tdTomato and Calb1 with the lumbar DRG sections of vehicle or DTA-treated mice. O Quantification of the double positive neurons per DRG section showed a significant decrease in those co-expressing Ret (p = 0.0002) and Calb1 (p = 0.004) but not Ntrk2 (p = 0.16). 4 sections per mouse, n = 3 mice. Scale bar represents 50 μm in all micrographs. Error bars represent Mean ± S.E.M. Unpaired, two-tailed Mann-Whitney test. **p < 0.01, ****p < 0.0001, ns = non-significant. Source data are provided as a Source Data file.