RESEARCH: Transgenic Mouse Model of Tauopathies with Glial Pathology and Nervous System Degeneration

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Neuron

Volume 35, Issue 3, 1 August 2002, Pages 433-446

Article

Transgenic Mouse Model of Tauopathies with Glial Pathology and Nervous

System Degeneration

Makoto Higuchi1, Takeshi Ishihara1, Bin Zhang1, Ming Hong1, Athena

dis2, Q. Trojanowski1 and Virginia M. -Y. Lee, , 1

1 Center for Neurodegenerative Disease Research, Department of Pathology and

Laboratory Medicine, University of Pennsylvania School of Medicine,

Philadelphia, PA 19104, USA

2 Department of Biomedical Sciences, E.K. Shriver Center for Mental

Retardation, Waltham, MA 02254, USA

Received 24 April 2002; revised 1 July 2002. Available online 6 August

2002.

Abstract

Frontotemporal dementias (FTDs), including corticobasal degeneration (CBD)

and progressive supranuclear palsy (PSP), are neurodegenerative tauopathies

characterized by widespread CNS neuronal and glial tau pathologies, but

there are no tau transgenic (Tg) mice that model neurodegeneration with glia

tau lesions. Thus, we generated Tg mice overexpressing human tau in neurons

and glia. No neuronal tau aggregates were detected, but old mice developed

Thioflavin S- and Gallyas-positive glial tau pathology resembling CBD

astrocytic plaques. Tau-immunoreactive and Gallyas-positive oligodendroglial

coiled bodies (similar to CBD and PSP), glial degeneration, and motor

deficits were associated with age-dependent accumulations of insoluble

hyperphosphorylated human tau and tau immunopositive filaments in

degenerating glial cells. Thus, tau-positive glial lesions similar to human

FTDs occur in these Tg mice, and these pathologies are linked to glial and

axonal degeneration.

Correspondence: Virginia M.-Y. Lee, (phone),

(fax); email: vmylee@...

Neuron

Volume 35, Issue 3, 1 August 2002, Pages 433-446