Factors other than hTau overexpression that contribute to tauopathy-like phenotype in rTg4510 mice

Dataset

Title Factors other than hTau overexpression that contribute to tauopathy-like phenotype in rTg4510 mice
Authors Gamache Julia, Benzow Kellie, Forster Colleen, Kemper Lisa, Hlynialuk Chris, Furrow Eva, Ashe Karen H., Koob Michael D.,
Description The tauopathy-like phenotype observed in the rTg4510 mouse line, in which human tauP301L expression specifically within the forebrain can be temporally controlled, has largely been attributed to high overexpression of mutant human tau in the forebrain region. Unexpectedly, we found that in a different mouse line with a targeted-insertion of the same transgene driven by the same tetracycline-TransActivator (tTA) allele, but with even higher overexpression of tauP301L than rTg4510, atrophy and tau histopathology are delayed, and a different behavioral profile is observed. This suggests that it is not overexpression of mutant human tau alone that contributes to the phenotype in rTg4510 mice. Furthermore we show that the tauopathy-like phenotype seen in rTg4510 requires a ~70-copy tau-transgene insertion in a 244kb deletion in Fgf14, a ~7-copy tTA- transgene insertion in a 508kb deletion that disrupts another five genes, in addition to high transgene overexpression. We propose that these additional effects need to be accounted for in any studies using rTg4510, and that Tg-INDEL mutations and their impacts on phenotype should be defined for all transgenic models used in biomedical research.
License Creative Commons CC0 1.0 Public Domain Dedication (https://creativecommons.org/publicdomain/zero/1.0/)
References
Funding
Keywords Neuroscience
Transgene
rTg4510
Tau
Fgf14
Data This dataset can be browsed online here or downloaded as a zip archive (1 MB). The current version of the dataset repository, possibly with updates, can be found here.
DOI 10.12751/g-node.3730d0
Citation This dataset can be cited as:
Gamache J, Benzow K, Forster C, Kemper L, Hlynialuk C, Furrow E, Ashe K, Koob M, (2019) Factors other than hTau overexpression that contribute to tauopathy-like phenotype in rTg4510 mice. G-Node. doi:10.12751/g-node.3730d0
Please also consider citing the material listed in the references
Resource Type Source Data