Bulk neocortical RNA sequencing of rNLS8 mice (on mixed C57BL/6J × C3H/HeJ background ) +/- active immunization with C-terminal hTDP-43 antigens

This data set reports RNA sequencing results obtained from whole cerebral cortices of NEFH-tTa/tetO-hTDP43∆NLS transgenic (“rNLS8”) mice that were actively immunized with C-terminal fragments of the human TDP-43 protein. The widely used rNLS8 mouse model overexpresses cytoplasmically mislocalized human TDP-43 in a doxycycline-inducible manner, mimicking ALS/FTD-like CNS pathology and motor dysfunction (Walker et al., 2015). The purpose of this study was to evaluate the safety profile and therapeutic potential of various human TDP-43 epitopes (up to approximately 40 amino acids in length) which were used as antigens for active immunization in a rapidly progressing mouse model of TDP-43 proteinopathy. To this end, we pre-screened 15 peptide antigens, collectively spanning the entire TDP-43 protein sequence, for immunogenicity and safety. Next, we repeatedly immunized “rNLS8” mice with the most promising antigens prior to transgene induction, and performed bulk RNA sequencing of the neocortex, since this region is considerably affected by TDP-43 pathology in both humans and the mouse model. We asked whether active immunization with two different peptide combinations leading to high antibody titers would affect – i.e. prevent – transcriptional alterations upon transgene induction. In summary, we provide a bulk neocortical gene expression profile of actively immunized (and mock-treated) ALS/FTD-resembling “rNLS8” mice. mRNA profiles from whole cerebral cortices of adult rNLS8 mice with a mixed C57BL/6J x C3H/HeJ background. Mice heterozygous for both the NEFH-tTa and the tetO-hTDP43∆NLS allele are referred to as “bigenic”, while “monogenic” mice (carrying only one tetO-hTDP43∆NLS allele) served as asymptomatic controls. The data set includes four different treatment groups: TDP-10+12: bigenic, treatment with combined peptides 10 and 12 (n=10); TDP-15: bigenic, treatment with peptide number 15 (n=12); TDP-PBS: sham treatment with PBS only (n=10); ctrl-PBS: monogenic, sham treatment with PBS only (n=17).