An Optimization of AAV-82Q-Delivered Rat Model of Huntington's Disease

• Published in: Journal of Korean Neurosurgical Society Vol. 63; no. 5; pp. 579 - 589
• Main Authors: So, Kyoung-Ha, Choi, Jai Ho, Islam, Jaisan, KC, Elina, Moon, Hyeong Cheol, Won, So Yoon, Kim, Hyong Kyu, Kim, Soochong, Hyun, Sang-Hwan, Park, Young Seok
• Format: Journal Article
• Language: Korean
• Published: 2020
• Subjects: Gene delivery; Neurodegenerative diseases; Huntington disease; Huntingtin protein; Adeno-associated virus vector
• ISSN: 2005-3711; 1598-7876

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.