Deletion of murine tau gene increases tau aggregation in a human mutant tau transgenic mouse model.
We have reported previously a tau transgenic mouse model (Tg30tau) overexpressing human 4R1N double-mutant tau (P301S and G272V) and that develops AD (Alzheimer's disease)-like NFTs (neurofibrillary tangles) in an age-dependent manner. Since murine tau might interfere with the toxic effects of human mutant tau, we set out to analyse the phenotype of our Tg30tau model in the absence of endogenous murine tau with the aim to reproduce more faithfully a model of human tauopathy. By crossing the Tg30tau line with TauKO (tau-knockout) mice, we have obtained a new mouse line called Tg30xTauKO that expresses only exogenous human double-mutant 4R1N tau. Whereas Tg30xTauKO mice express fewer tau proteins compared with Tg30tau, they exhibit augmented sarkosyl-insoluble tau in the brain and an increased number of Gallyas-positive NFTs in the hippocampus. Taken together, exclusion of murine tau causes accelerated tau aggregation during aging of this mutant tau transgenic model.
Ando
Kunie
K
Laboratory of Histology, Neuroanatomy and Neuropathology, Université Libre de Bruxelles, 808 route de Lennik, B-1070 Brussels, Belgium. kuniando@ulb.ac.be
Leroy
Karelle
K
Heraud
Céline
C
Kabova
Anna
A
Yilmaz
Zehra
Z
Authelet
Michèle
M
Suain
Valèrie
V
De Decker
Robert
R
Brion
Jean-Pierre
JP
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000818:Animals; D011232:Chemical Precipitation; D004195:Disease Models, Animal; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D050505:Mutant Proteins / Q000378:metabolism / Q000502:physiology; D055503:Protein Multimerization / Q000235:genetics / Q000502:physiology; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism*
D050505:Mutant Proteins; D016875:tau Proteins