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http://dx.doi.org/10.3340/jkns.2019.0182

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

So, Kyoung-Ha (Institute for Stem Cell & Regenerative Medicine (ISCRM), Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University)
Choi, Jai Ho (Department of Neurosurgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Islam, Jaisan (Department of Medical Neuroscience, College of Medicine, Chungbuk National University)
KC, Elina (Department of Medical Neuroscience, College of Medicine, Chungbuk National University)
Moon, Hyeong Cheol (Department of Medical Neuroscience, College of Medicine, Chungbuk National University)
Won, So Yoon (Department of Biochemistry and Medical Research Center, Chungbuk National University)
Kim, Hyong Kyu (Department of Biochemistry and Medical Research Center, Chungbuk National University)
Kim, Soochong (Laboratory of Veterinary Pathology, College of Veterinary Medicine, Chungbuk National University)
Hyun, Sang-Hwan (Institute for Stem Cell & Regenerative Medicine (ISCRM), Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University)
Park, Young Seok (Institute for Stem Cell & Regenerative Medicine (ISCRM), Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University)
Publication Information
Journal of Korean Neurosurgical Society / v.63, no.5, 2020 , pp. 579-589 More about this Journal
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.
Keywords
Huntington disease; Adeno-associated virus vector; Huntingtin protein; Neurodegenerative diseases; Gene delivery;
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