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Gait Ignition Failure in JNPL3 Human Tau-mutant Mice

Title
Gait Ignition Failure in JNPL3 Human Tau-mutant Mice
Authors
Jang, HoChungRyu, Jung HwaShin, Kyung MinSeo, Na-youngKim, Gyu HyunHuh, Yang HoonPae, Ae NimLee, Kye Joo
Issue Date
2019-06
Citation
Experimental Neurobiology, 28(3), 404-413
Type
Article
Article Type
Article
Author Keywords
TauGait ignitionMotor behaviorNeurodegenerative diseaseTauopathy
Keywords
NEUROFIBRILLARY TANGLESPARKINSONS-DISEASEMOUSE MODELL-THREO-3,4-DIHYDROXYPHENYLSERINEASSOCIATION
ISSN
1226-2560
Abstract
Cognitive impairments and motor dysfunction are commonly observed behavioral phenotypes in genetic animal models of neurodegenerative diseases. JNPL3 transgenic mice expressing human P301L-mutant tau display motor disturbances with age- and gene dose-dependent development of neurofibrillary tangles, suggesting that tau pathology causes neurodegeneration associated with motor behavioral abnormalities. Although gait ignition failure (GIF), a syndrome marked by difficulty in initiating locomotion, has been described in patients with certain forms of tauopathies, transgenic mouse models mirroring human GIF syndrome have yet to be reported. Using the open field and balance beam tests, here we discovered that JNPL3 homozygous mice exhibit a marked delay of movement initiation. The elevated plus maze excluded the possibility that hesitation to start in JNPL3 mice was caused by enhanced levels of anxiety. Considering the normal gait ignition in rTg4510 mice expressing the same mutant tau in the forebrain, GIF in JNPL3 mice seems to arise from abnormal tau deposition in the hindbrain areas involved in locomotor initiation. Accordingly, immunohistochemistry revealed highly phosphorylated paired helical filament tau in JNPL3 brainstem areas associated with gait initiation. Together, these findings demonstrate a novel behavioral phenotype of impaired gait initiation in JNPL3 mice and underscore the value of this mouse line as a tool to study the neural mechanisms and potential treatments for human GIF syndrome. Copyright © Experimental Neurobiology 2019.
URI
http://hdl.handle.net/20.500.11750/10393
DOI
10.5607/en.2019.28.3.404
Publisher
Korean Society for Neurodegenerative Disease
Files:
There are no files associated with this item.
Collection:
ETC1. Journal Articles


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