Transgenic mouse model of tauopathies with glial pathology and nervous system degeneration.
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.
Higuchi
Makoto
M
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Ishihara
Takeshi
T
Zhang
Bin
B
Hong
Ming
M
Andreadis
Athena
A
Trojanowski
John
J
Lee
Virginia M-Y
VM
D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D016923:Cell Death / Q000235:genetics; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009069:Movement Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009420:Nervous System / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D024801:Tauopathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018911:Trinucleotide Repeats / Q000235:genetics; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D020033:Protein Isoforms; D016875:tau Proteins