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@MISC{Riemenschneider:258264,
author = {Riemenschneider, Henrick and Edbauer, Dieter},
title = {{D}ataset: {B}ulk neocortical {RNA} sequencing of r{NLS}8
mice (on mixed {C}57{BL}/6{J} × {C}3{H}/{H}e{J} background
) +/- active immunization with {C}-terminal h{TDP}-43
antigens},
publisher = {Gene Expression Omnibus},
reportid = {DZNE-2023-00610},
year = {2023},
abstract = {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.},
cin = {AG Edbauer},
cid = {I:(DE-2719)1110004},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)32},
url = {https://pub.dzne.de/record/258264},
}