Academic Journal
Production of Spinocerebellar Ataxia Type 3 Model Mice by Intravenous Injection of AAV-PHP.B Vectors
| العنوان: | Production of Spinocerebellar Ataxia Type 3 Model Mice by Intravenous Injection of AAV-PHP.B Vectors |
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| المؤلفون: | Ayumu Konno, Yoichiro Shinohara, Hirokazu Hirai |
| المصدر: | International Journal of Molecular Sciences, Vol 25, Iss 13, p 7205 (2024) |
| بيانات النشر: | MDPI AG |
| سنة النشر: | 2024 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | adeno-associated virus, AAV, AAV-PHP.B, Spinocerebellar ataxia type 3, SCA3, Machado–Joseph disease, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | We aimed to produce a mouse model of spinocerebellar ataxia type 3 (SCA3) using the mouse blood–brain barrier (BBB)-penetrating adeno-associated virus (AAV)-PHP.B. Four-to-five-week-old C57BL/6 mice received injections of high-dose (2.0 × 10 11 vg/mouse) or low-dose (5.0 × 10 10 vg/mouse) AAV-PHP.B encoding a SCA3 causative gene containing abnormally long 89 CAG repeats [ATXN3(Q89)] under the control of the ubiquitous chicken β-actin hybrid (CBh) promoter. Control mice received high doses of AAV-PHP.B encoding ATXN3 with non-pathogenic 15 CAG repeats [ATXN3(Q15)] or phosphate-buffered saline (PBS) alone. More than half of the mice injected with high doses of AAV-PHP.B encoding ATXN3(Q89) died within 4 weeks after the injection. No mice in other groups died during the 12-week observation period. Mice injected with low doses of AAV-PHP.B encoding ATXN3(Q89) exhibited progressive motor uncoordination starting 4 weeks and a shorter stride in footprint analysis performed at 12 weeks post-AAV injection. Immunohistochemistry showed thinning of the molecular layer and the formation of nuclear inclusions in Purkinje cells from mice injected with low doses of AAV-PHP.B encoding ATXN3(Q89). Moreover, ATXN3(Q89) expression significantly reduced the number of large projection neurons in the cerebellar nuclei to one third of that observed in mice expressing ATXN3(Q15). This AAV-based approach is superior to conventional methods in that the required number of model mice can be created simply by injecting AAV, and the expression levels of the responsible gene can be adjusted by changing the amount of AAV injected. Moreover, this method may be applied to produce SCA3 models in non-human primates. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/25/13/7205; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067; https://doaj.org/article/6da3aff01b2e4481bb50316fbac6750e |
| DOI: | 10.3390/ijms25137205 |
| الاتاحة: | https://doi.org/10.3390/ijms25137205 https://doaj.org/article/6da3aff01b2e4481bb50316fbac6750e |
| رقم الانضمام: | edsbas.2165C8CC |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms25137205 |