Pathogenic tau recruits wild-type tau into brain inclusions and induces gut degeneration in transgenic SPAM mice.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
12 05 2022
12 05 2022
Historique:
received:
01
12
2021
accepted:
14
04
2022
entrez:
13
5
2022
pubmed:
14
5
2022
medline:
18
5
2022
Statut:
epublish
Résumé
Pathological tau inclusions are neuropathologic hallmarks of many neurodegenerative diseases. We generated and characterized a transgenic mouse model expressing pathogenic human tau with S320F and P301S aggregating mutations (SPAM) at transgene levels below endogenous mouse tau protein levels. This mouse model develops a predictable temporal progression of tau pathology in the brain with biochemical and ultrastructural properties akin to authentic tau inclusions. Surprisingly, pathogenic human tau extensively recruited endogenous mouse tau into insoluble aggregates. Despite the early onset and rapid progressive nature of tau pathology, major neuroinflammatory and transcriptional changes were only detectable at later time points. Moreover, tau SPAM mice are the first model to develop loss of enteric neurons due to tau accumulation resulting in a lethal phenotype. With moderate transgene expression, rapidly progressing tau pathology, and a highly predictable lethal phenotype, the tau SPAM model reveals new associations of tau neurotoxicity in the brain and intestinal tract.
Identifiants
pubmed: 35550593
doi: 10.1038/s42003-022-03373-1
pii: 10.1038/s42003-022-03373-1
pmc: PMC9098443
doi:
Substances chimiques
MAPT protein, human
0
tau Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
446Subventions
Organisme : NIA NIH HHS
ID : F30 AG067673
Pays : United States
Informations de copyright
© 2022. The Author(s).
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