An Optimization of AAV-82Q-Delivered Rat Model of Huntington’s Disease
- Author:
Kyoung-Ha SO
1
;
Jai Ho CHOI
;
Jaisan ISLAM
;
Elina KC
;
Hyeong Cheol MOON
;
So Yoon WON
;
Hyong Kyu KIM
;
Soochong KIM
;
Sang-Hwan HYUN
;
Young Seok PARK
Author Information
- Publication Type:Laboratory Investigation
- From:Journal of Korean Neurosurgical Society 2020;63(5):579-589
- CountryRepublic of Korea
- Language:0
-
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.
