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Dataset

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

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  1. 1N. Bud Grossman Center for Memory Research and Care, Department of Neurology, University of Minnesota, Minneapolis, MN 55414
  2. 2Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55414
  3. 3Histology & Research Laboratory, Clinical and Translational Science Institute, University of Minnesota, Minneapolis, 55414
  4. 4Veterinary Clinical Sciences (College of Veterinary Medicine), University of Minnesota, Minneapolis, MN 55414

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Published 29 Mar. 2019 | License Creative Commons CC0 1.0 Public Domain Dedication

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.

Keywords

| Neuroscience | Transgene | rTg4510 | Tau | Fgf14 |

References

  • Gamache J, Benzow K, Forster C, Kemper L, Hlynialuk C, Furrow E, Ashe KH, Koob MD (2019) Factors other than hTau overexpression that contribute to tauopathy-like phenotype in rTg4510 mice. Nat Commun 10(1):2479. .

Citation

Gamache J, Benzow K, Forster C, Kemper L, Hlynialuk C, Furrow E, Ashe KH, Koob MD (2019) Factors other than hTau overexpression that contribute to tauopathy-like phenotype in rTg4510 mice. G-Node. https://doi.org/10.12751/g-node.3730d0