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Cited by 7Alzheimer's disease research and treatmentsAmyotrophic Lateral Sclerosis ResearchNeuroinflammation and Neurodegeneration Mechanisms

Differential accumulation of tau pathology between reciprocal F1 hybrids of rTg4510 mice

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Yanagisawa, Daijiro, Hamezah, Hamizah Shahirah, Pahrudin Arrozi, Aslina, Tooyama, Ikuo·2021·Scientific Reports
DOI 10.1038/s41598-021-89142-2PMC PMC8100160
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Abstract

Tau, a family of microtubule-associated proteins, forms abnormal intracellular inclusions, so-called tau pathology, in a range of neurodegenerative diseases collectively known as tauopathies. The rTg4510 mouse model is a well-characterized bitransgenic F1 hybrid mouse model of tauopathy, which was obtained by crossing a Camk2α-tTA mouse line (on a C57BL/6 J background) with a tetO-MAPT*P301L mouse line (on a FVB/NJ background). The aim of this study was to investigate the effects of the genetic background and sex on the accumulation of tau pathology in reciprocal F1 hybrids of rTg4510 mice, i.e., rTg4510 on the (C57BL/6 J × FVB/NJ)F1 background (rTg4510_CxF) and on the (FVB/NJ × C57BL/6 J)F1 background (rTg4510_FxC). As compared with rTg4510_CxF mice, the rTg4510_FxC mice showed marked levels of tau pathology in the forebrain. Biochemical analyses indicated that the accumulation of abnormal tau species was accelerated in rTg4510_FxC mice. There were strong effects of the genetic background on the differential accumulation of tau pathology in rTg4510 mice, while sex had no apparent effect. Interestingly, midline-1 (Mid1) was identified as a candidate gene associated with this difference and exhibited significant up/downregulation according to the genetic background. Mid1 silencing with siRNA induced pathological phosphorylation of tau in HEK293T cells that stably expressed human tau with the P301L mutation, suggesting the role of Mid1 in pathological alterations of tau. Elucidation of the underlying mechanisms will provide novel insights into the accumulation of tau pathology and is expected to be especially informative to researchers for the continued development of therapeutic interventions for tauopathies.

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  • Previously, genetic background has been shown to influence the amount of tau and the presence of at least one phospho-epitope in tau transgenic models.

    “Previously, genetic background has been shown to influence the amount of tau and the presence of at least one phospho-epitope in tau transgenic models (Eskandari-Sedighi et al., 2017; Yanagisawa et al., 2021; Bailey et al., 2014).”

    From Network analysis identifies strain-dependent response to tau and tau seeding-associated genes (2023) · cites this paper as Yanagisawa et al., 2021

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Authors
Yanagisawa, D., Hamezah, H. S., Pahrudin Arrozi, A., & Tooyama, I.
Affiliations
Shiga University of Medical Science (JP)
Corresponding author
  • Yanagisawa, Daijiro
  • Tooyama, Ikuo
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2021-05-05
Volume
11
Issue
1
Pages
9623-9623
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-021-89142-2
PMC
PMC8100160
OpenAlex
W3159551175
Cited by
7
References
3
Citations by year
2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 1
FWCI
0.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Japan Society for the Promotion of Science (JP17K01355, JP17H03560)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
tau pathology, tauopathy, rTg4510 mice, reciprocal F1 hybrids, genetic background effects, sex differences, MID1, tau phosphorylation, P301L tau mutation, forebrain, siRNA knockdown
MeSH terms
Animals, Brain, Inclusion Bodies, Disease Models, Animal, Mice, Transgenic, Neurons, Phosphorylation, tau Proteins, Tauopathies, Mice

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