Abstract
Tau belongs to the microtubule-associated family of proteins that maintain cytoskeletal structure by regulating microtubule dynamics. In certain neurodegenerative diseases termed tauopathies, tau is abnormally phosphorylated and accumulates as filamentous inclusions. Transgenic mouse models that overexpress human tau have been widely used to investigate tau pathogenesis. Although many studies have attempted to elucidate the pathological function of transgenic human tau, it remains unknown whether endogenous mouse tau is involved in disease progression. Here we generated an mTau antibody that selectively recognizes mouse and rat tau, but not human tau. In rTg4510 tau transgenic mice, we identified a higher molecular weight mouse tau (~60-kDa) in sarkosyl-insoluble fractions. mTau antibody started to recognize intracellular aggregates and thread-like structures in 4- to 6-month-old rTg4510 mice. Tau inclusions appeared earlier, being detected in 2.5-month-old rTg4510 mice with MC1 antibody. Immunoelectron microscopy confirmed the presence of filamentous aggregates of mouse tau, which were abundant in oligodendrocytes but rare in neurons. Mouse tau inclusions in oligodendrocytes were confirmed by double-labeling with an oligodendrocyte marker. Our data indicate that mouse tau has potential aggregation properties in neurons and non-neurons. The mTau antibody will be useful for investigating the role of mouse tau in mouse models of tauopathy.
Original language | English (US) |
---|---|
Pages (from-to) | 589-600 |
Number of pages | 12 |
Journal | Journal of Alzheimer's Disease |
Volume | 38 |
Issue number | 3 |
DOIs | |
State | Published - 2014 |
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Keywords
- Antibody
- mouse tau
- oligodendrocytes
- tau protein
- tauopathy
- transgenic mice
ASJC Scopus subject areas
- Psychiatry and Mental health
- Geriatrics and Gerontology
- Clinical Psychology
Cite this
Endogenous tau aggregates in oligodendrocytes of rTg4510 mice induced by human P301L tau. / Ren, Yan; Lin, Wen Lang; Sanchez, Laura; Ceballos, Carolina; Polydoro, Manuela; Spires-Jones, Tara L.; Hyman, Bradley T.; Dickson, Dennis W; Sahara, Naruhiko.
In: Journal of Alzheimer's Disease, Vol. 38, No. 3, 2014, p. 589-600.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endogenous tau aggregates in oligodendrocytes of rTg4510 mice induced by human P301L tau
AU - Ren, Yan
AU - Lin, Wen Lang
AU - Sanchez, Laura
AU - Ceballos, Carolina
AU - Polydoro, Manuela
AU - Spires-Jones, Tara L.
AU - Hyman, Bradley T.
AU - Dickson, Dennis W
AU - Sahara, Naruhiko
PY - 2014
Y1 - 2014
N2 - Tau belongs to the microtubule-associated family of proteins that maintain cytoskeletal structure by regulating microtubule dynamics. In certain neurodegenerative diseases termed tauopathies, tau is abnormally phosphorylated and accumulates as filamentous inclusions. Transgenic mouse models that overexpress human tau have been widely used to investigate tau pathogenesis. Although many studies have attempted to elucidate the pathological function of transgenic human tau, it remains unknown whether endogenous mouse tau is involved in disease progression. Here we generated an mTau antibody that selectively recognizes mouse and rat tau, but not human tau. In rTg4510 tau transgenic mice, we identified a higher molecular weight mouse tau (~60-kDa) in sarkosyl-insoluble fractions. mTau antibody started to recognize intracellular aggregates and thread-like structures in 4- to 6-month-old rTg4510 mice. Tau inclusions appeared earlier, being detected in 2.5-month-old rTg4510 mice with MC1 antibody. Immunoelectron microscopy confirmed the presence of filamentous aggregates of mouse tau, which were abundant in oligodendrocytes but rare in neurons. Mouse tau inclusions in oligodendrocytes were confirmed by double-labeling with an oligodendrocyte marker. Our data indicate that mouse tau has potential aggregation properties in neurons and non-neurons. The mTau antibody will be useful for investigating the role of mouse tau in mouse models of tauopathy.
AB - Tau belongs to the microtubule-associated family of proteins that maintain cytoskeletal structure by regulating microtubule dynamics. In certain neurodegenerative diseases termed tauopathies, tau is abnormally phosphorylated and accumulates as filamentous inclusions. Transgenic mouse models that overexpress human tau have been widely used to investigate tau pathogenesis. Although many studies have attempted to elucidate the pathological function of transgenic human tau, it remains unknown whether endogenous mouse tau is involved in disease progression. Here we generated an mTau antibody that selectively recognizes mouse and rat tau, but not human tau. In rTg4510 tau transgenic mice, we identified a higher molecular weight mouse tau (~60-kDa) in sarkosyl-insoluble fractions. mTau antibody started to recognize intracellular aggregates and thread-like structures in 4- to 6-month-old rTg4510 mice. Tau inclusions appeared earlier, being detected in 2.5-month-old rTg4510 mice with MC1 antibody. Immunoelectron microscopy confirmed the presence of filamentous aggregates of mouse tau, which were abundant in oligodendrocytes but rare in neurons. Mouse tau inclusions in oligodendrocytes were confirmed by double-labeling with an oligodendrocyte marker. Our data indicate that mouse tau has potential aggregation properties in neurons and non-neurons. The mTau antibody will be useful for investigating the role of mouse tau in mouse models of tauopathy.
KW - Antibody
KW - mouse tau
KW - oligodendrocytes
KW - tau protein
KW - tauopathy
KW - transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=84889683194&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84889683194&partnerID=8YFLogxK
U2 - 10.3233/JAD-130986
DO - 10.3233/JAD-130986
M3 - Article
C2 - 24028867
AN - SCOPUS:84889683194
VL - 38
SP - 589
EP - 600
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 3
ER -