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

ABSTRACT: 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 244?kb deletion in Fgf14, a ~7-copy tTA-transgene insertion in a 508?kb 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.

SUBMITTER: Gamache J

PROVIDER: S-EPMC6554306 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Gamache Julia J Benzow Kellie K Forster Colleen C Kemper Lisa L Hlynialuk Chris C Furrow Eva E Ashe Karen H KH Koob Michael D MD

Nature communications 20190606 1

The tauopathy-like phenotype observed in the rTg4510 mouse line, in which human tau<sub>P301L</sub> 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, atro ...[more]

PMID: 31171783

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

Publications

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

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