A novel tauopathy model mimicking molecular and spatial aspects of human tau pathology.

Autor:	Yanai R; Advanced Neuroimaging Center, Institute for Quantum Medical Sciences, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan., Mitani TT; Laboratory for Synthetic Biology, RIKEN BDR, Suita, Osaka, 565-0871, Japan.; Department of Systems Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.; Department of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan., Susaki EA; Laboratory for Synthetic Biology, RIKEN BDR, Suita, Osaka, 565-0871, Japan.; Department of Biochemistry and Systems Biomedicine, Graduate School of Medicine, Juntendo University, Tokyo, 113-8421, Japan.; Nakatani Biomedical Spatialomics Hub, Graduate School of Medicine, Juntendo University, Tokyo, 113-8421, Japan., Minamihisamatsu T; Advanced Neuroimaging Center, Institute for Quantum Medical Sciences, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan., Shimojo M; Advanced Neuroimaging Center, Institute for Quantum Medical Sciences, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan., Saito Y; Department of Biochemistry and Systems Biomedicine, Graduate School of Medicine, Juntendo University, Tokyo, 113-8421, Japan., Mizuma H; Advanced Neuroimaging Center, Institute for Quantum Medical Sciences, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan., Nitta N; Advanced Neuroimaging Center, Institute for Quantum Medical Sciences, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan., Kaneda D; Department of Neuropathology, Choju Medical Institute, Fukushimura Hospital, Aichi, 441-8124, Japan., Hashizume Y; Department of Neuropathology, Choju Medical Institute, Fukushimura Hospital, Aichi, 441-8124, Japan., Matsumoto G; Department of Neurological Disease Control, Osaka Metropolitan University, School of Medicine, Osaka, 545-8585, Japan., Tanemura K; Laboratory of Animal Reproduction and Development, Graduate School of Agricultural Science, Tohoku University, Miyagi, 980-8572, Japan., Zhang MR; Department of Advanced Nuclear Medicine Science, Institute for Quantum Medical Sciences, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan., Higuchi M; Advanced Neuroimaging Center, Institute for Quantum Medical Sciences, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan., Ueda HR; Laboratory for Synthetic Biology, RIKEN BDR, Suita, Osaka, 565-0871, Japan.; Department of Systems Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.; Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan., Sahara N; Advanced Neuroimaging Center, Institute for Quantum Medical Sciences, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan.
Jazyk:	angličtina
Zdroj:	Brain communications [Brain Commun] 2024 Sep 19; Vol. 6 (5), pp. fcae326. Date of Electronic Publication: 2024 Sep 19 (Print Publication: 2024).
DOI:	10.1093/braincomms/fcae326
Abstrakt:	Creating a mouse model that recapitulates human tau pathology is essential for developing strategies to intervene in tau-induced neurodegeneration. However, mimicking the pathological features seen in human pathology often involves a trade-off with artificial effects such as unexpected gene insertion and neurotoxicity from the expression system. To overcome these issues, we developed the rTKhomo mouse model by combining a transgenic CaMKII-tTA system with a P301L mutated 1N4R human tau knock-in at the Rosa26 locus with a C57BL/6J background. This model closely mimics human tau pathology, particularly in the hippocampal CA1 region, showing age-dependent tau accumulation, neuronal loss and neuroinflammation. Notably, whole-brain 3D staining and light-sheet microscopy revealed a spatial gradient of tau deposition from the entorhinal cortex to the hippocampus, similar to the spatial distribution of Braak neurofibrillary tangle staging. Furthermore, [ 18 F]PM-PBB3 positron emission tomography imaging enabled the quantification and live monitoring of tau deposition. The rTKhomo mouse model shows potential as a promising next-generation preclinical tool for exploring the mechanisms of tauopathy and for developing interventions targeting the spatial progression of tau pathology. Competing Interests: M.H. hold patents on compound related to the present report (JP5422782/EP12884742.3/CA2894994/HK1208672). H.R.U. is a founder of CUBICStars, Inc. that offers services based on CUBIC technology. E.A.S. is employed by the company. E.A.S. and H.R.U. are co-inventors on patents and patent applications owned by RIKEN and CUBICStars, Inc., covering the CUBIC reagents and CUBIC-HV kits, respectively. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
Databáze:	MEDLINE
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