|
KMID : 1001920200630050579
|
|
Journal of Korean Neurosurgical Society
2020 Volume.63 No. 5 p.579 ~ p.589
|
|
|
An Optimization of AAV-82Q-Delivered Rat Model of Huntington’s Disease
|
|
So Kyoung-Ha
Choi Jai-Ho
Islam Jaisan
Elina K. C.
Moon Hyeong-Cheol
Won So-Yoon
Kim Hyong-Kyu
Kim Soo-Chong
Hyun Sang-Hwan
Park Young-Seok
|
|
|
Abstract
|
|
|
Objective: No optimum genetic rat Huntington model both neuropathological using an adeno-associated virus (AAV-2) vector vector has been reported to date. We investigated whether direct infection of an AAV2 encoding a fragment of mutant huntingtin (AV2-82Q) into the rat striatum was useful for optimizing the Huntington rat model.
Methods: We prepared ten unilateral models by injecting AAV2-82Q into the right striatum, as well as ten bilateral models. In each group, five rats were assigned to either the 2×1012 genome copies (GC)/mL of AAV2-82Q (×1, low dose) or 2×1013 GC/mL of AAV2-82Q (×10, high dose) injection model. Ten unilateral and ten bilateral models injected with AAV-empty were also prepared as control groups. We performed cylinder and stepping tests 2, 4, 6, and 8 weeks after injection, tested EM48 positive mutant huntingtin aggregates.
Results: The high dose of unilateral and bilateral AAV2-82Q model showed a greater decrease in performance on the stepping and cylinder tests. We also observed more prominent EM48-positive mutant huntingtin aggregates in the medium spiny neurons of the high dose of AAV2-82Q injected group.
Conclusion: Based on the results from the present study, high dose of AAV2-82Q is the optimum titer for establishing a Huntington rat model. Delivery of high dose of human AAV2-82Q resulted in the manifestation of Huntington behaviors and optimum expression of the huntingtin protein in vivo.
|
|
|
KEYWORD
|
|
|
Huntington disease, Adeno-associated virus vector, Huntingtin protein, Neurodegenerative diseases, Gene delivery
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
   
|