TY - JOUR
T1 - Ultrastructural neuronal pathology in transgenic mice expressing mutant (P301L) human tau
AU - Lin, Wen Lang
AU - Lewis, Jada
AU - Yen, Shu Hui
AU - Hutton, Michael
AU - Dickson, Dennis W.
N1 - Funding Information:
The authors express their gratitude to Drs. Peter Davies, Albert Einstein College of Medicine, Bronx, NY, Hanna Ksiezak-Reding, Mt. Sinai School of Medicine, New York, NY, for their generous donation of tau and ubiquitin antibodies, and Dr. D. Borchelt, Johns Hopkins University, Baltimore, MD for the Mo PrP vector. Supported by: NIH AG16574, AG17216, AG14449, AG03949, the Mayo Foundation, and the Smith Scholar Program.
PY - 2003/11
Y1 - 2003/11
N2 - Transgenic mice expressing mutant (P301L) human tau develop neurofibrillary tangles, amyotrophy and progressive motor disturbance. We present ultrastructural features of neuronal degeneration in this model that suggests involvement of both neurofibrillary and autophagic processes in neurodegeneration. Neurons undergoing neurofibrillary degeneration contain tau-immunoreactive, 15-20 nm-wide straight or wavy filaments with no periodic twists. Tau filaments were found in two types of affected neurons. One type resembled neurons with neurofibrillary tangles (NFT) that were filled with numerous filaments that displaced sparse cytoplasmic organelles to the periphery. Microtubules were almost completely absent. The nucleus remained centrally located, but showed lobulations due to deep infoldings. The other type resembled ballooned neurons seen in some human tauopathies. The nucleus was peripherally placed, but normal appearing. The cytoplasmic organelles were dispersed throughout the swollen perikarya, the Golgi complex was fragmented and duplicated, while mitochondria and other organelles appeared normal. Tau filaments similar to those in NFT were sparse and not tightly packed. Microtubules were also sparse. Many autophagic vacuoles were present in these cells. Heterogeneous appearing axonal swellings resembling spheroids in human tauopathies were present in gray and white matter. Unlike normal appearing axons, axonal spheroids were filled with tau-immunoreactive filaments and autophagic vacuoles, in addition to normal appearing neurofilaments and microtubules. These P301L transgenic mice exhibit many features common to human tauopathies, making them a valuable model to study the pathogenesis of these uncommon disorders.
AB - Transgenic mice expressing mutant (P301L) human tau develop neurofibrillary tangles, amyotrophy and progressive motor disturbance. We present ultrastructural features of neuronal degeneration in this model that suggests involvement of both neurofibrillary and autophagic processes in neurodegeneration. Neurons undergoing neurofibrillary degeneration contain tau-immunoreactive, 15-20 nm-wide straight or wavy filaments with no periodic twists. Tau filaments were found in two types of affected neurons. One type resembled neurons with neurofibrillary tangles (NFT) that were filled with numerous filaments that displaced sparse cytoplasmic organelles to the periphery. Microtubules were almost completely absent. The nucleus remained centrally located, but showed lobulations due to deep infoldings. The other type resembled ballooned neurons seen in some human tauopathies. The nucleus was peripherally placed, but normal appearing. The cytoplasmic organelles were dispersed throughout the swollen perikarya, the Golgi complex was fragmented and duplicated, while mitochondria and other organelles appeared normal. Tau filaments similar to those in NFT were sparse and not tightly packed. Microtubules were also sparse. Many autophagic vacuoles were present in these cells. Heterogeneous appearing axonal swellings resembling spheroids in human tauopathies were present in gray and white matter. Unlike normal appearing axons, axonal spheroids were filled with tau-immunoreactive filaments and autophagic vacuoles, in addition to normal appearing neurofilaments and microtubules. These P301L transgenic mice exhibit many features common to human tauopathies, making them a valuable model to study the pathogenesis of these uncommon disorders.
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U2 - 10.1023/B:NEUR.0000021904.61387.95
DO - 10.1023/B:NEUR.0000021904.61387.95
M3 - Article
C2 - 15044841
AN - SCOPUS:3442884830
SN - 0300-4864
VL - 32
SP - 1091
EP - 1105
JO - Journal of Neurocytology
JF - Journal of Neurocytology
IS - 9
ER -