 |
 Previous Article | Next Article 
The Journal of Neuroscience, August 15, 2001, 21(16):6026-6035
Attenuated Neurodegenerative Disease Phenotype in Tau Transgenic
Mouse Lacking Neurofilaments
Takeshi
Ishihara,
Makoto
Higuchi,
Bin
Zhang,
Yasumasa
Yoshiyama,
Ming
Hong,
John Q.
Trojanowski, and
Virginia M.-Y.
Lee
Center for Neurodegenerative Disease Research, Department of
Pathology and Laboratory Medicine, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania 19104
Previous studies have shown that transgenic (Tg) mice
overexpressing human tau protein develop filamentous tau aggregates in
the CNS. The most abundant tau aggregates are found in spinal cord and
brainstem in which they colocalize with neurofilaments (NFs) as
spheroids in axons. To elucidate the role of NF subunit proteins in tau
aggregate formation and to test the hypothesis that NFs are
pathological chaperones in the formation of intraneuronal tau
inclusions, we crossbred previously described tau (T44) Tg mice
overexpressing the smallest human tau isoform with knock-out mice
devoid of NFL (NFL /) or NFH (NFH/). Depletion of NF subunit proteins from the T44 mice (i.e., T44;NFL/ and T44;NFH/), in
particular NFL, resulted in a dramatic decrease in the total number of
tau-positive spheroids in spinal cord and brainstem. Concomitant with
the reduction in spheroid number, the bigenic mice showed delayed
accumulation of insoluble tau protein in the CNS, increased viability,
reduced weight loss, and improved behavioral phenotype when compared
with the single T44 Tg mice. These results imply that NFs are
pathological chaperones in the development of tau spheroids and suggest
a role for NFs in the pathogenesis of neurofibrillary tau lesions in
neurodegenerative disorders that contain both NFs and tau proteins.
Key words:
tau; neurofilaments; neurodegeneration; neurofibrillary
pathology; animal models; cytoskeleton
Copyright © 2001 Society for Neuroscience 0270-6474/01/21166026-10$05.00/0
This article has been cited by other articles:
|
|
|
|
 
J. Zhai, H. Lin, J.-P. Julien, and W. W. Schlaepfer
Disruption of neurofilament network with aggregation of light neurofilament protein: a common pathway leading to motor neuron degeneration due to Charcot Marie Tooth disease-linked mutations in NFL and HSPB1
Hum. Mol. Genet.,
December 15, 2007;
16(24):
3103 - 3116.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Leroy, A. Bretteville, K. Schindowski, E. Gilissen, M. Authelet, R. De Decker, Z. Yilmaz, L. Buee, and J.-P. Brion
Early Axonopathy Preceding Neurofibrillary Tangles in Mutant Tau Transgenic Mice
Am. J. Pathol.,
September 1, 2007;
171(3):
976 - 992.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Zhang, M. Higuchi, Y. Yoshiyama, T. Ishihara, M. S. Forman, D. Martinez, S. Joyce, J. Q. Trojanowski, and V. M.-Y. Lee
Retarded Axonal Transport of R406W Mutant Tau in Transgenic Mice with a Neurodegenerative Tauopathy
J. Neurosci.,
May 12, 2004;
24(19):
4657 - 4667.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Lin, J. Zhai, R. Canete-Soler, and W. W. Schlaepfer
3' Untranslated Region in a Light Neurofilament (NF-L) mRNA Triggers Aggregation of NF-L and Mutant Superoxide Dismutase 1 Proteins in Neuronal Cells
J. Neurosci.,
March 17, 2004;
24(11):
2716 - 2726.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Dou, W. J. Netzer, K. Tanemura, F. Li, F. U. Hartl, A. Takashima, G. K. Gouras, P. Greengard, and H. Xu
Chaperones increase association of tau protein with microtubules
PNAS,
January 21, 2003;
100(2):
721 - 726.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Stamer, R. Vogel, E. Thies, E. Mandelkow, and E.-M. Mandelkow
Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress
J. Cell Biol.,
March 18, 2002;
156(6):
1051 - 1063.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
