Generation of Transgenic Cynomolgus Monkeys Overexpressing the Gene for Amyloid-β Precursor Protein
| Autor: | Tomoyuki Tsukiyama, Yasunari Seita, Masanaga Muto, Masaki Nishimura, Chizuru Iwatani, Ikuo Tooyama, Hideaki Tsuchiya, Toshifumi Morimura, Naoki Watanabe, Toshiharu Suzuki, Shinichiro Nakamura, Daijiro Yanagisawa, Masatsugu Ema, Eiichi Okamura, Masataka Nakaya |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Genetically modified mouse zygote Amyloid Transgene primates cryopreservation Presenilin Animals Genetically Modified 03 medical and health sciences Amyloid beta-Protein Precursor 0302 clinical medicine Gene expression mental disorders Amyloid precursor protein medicine Animals animal Promoter Regions Genetic transgenic biology General Neuroscience Amyloid-beta protein precursor Neurodegeneration Brain General Medicine medicine.disease vitrification Cell biology Psychiatry and Mental health Clinical Psychology Disease Models Animal Macaca fascicularis 030104 developmental biology biology.protein intracytoplasmic sperm injection (ICSI) Tauopathy Geriatrics and Gerontology 030217 neurology & neurosurgery Research Article |
| Zdroj: | Journal of Alzheimer's Disease |
| ISSN: | 1875-8908 |
| Popis: | Alzheimer's disease (AD) is the most common cause of dementia and understanding its pathogenesis should lead to improved therapeutic and diagnostic methods. Although several groups have developed transgenic mouse models overexpressing the human amyloid-β precursor protein (APP) gene with AD mutations, with and without presenilin mutations, as well as APP gene knock-in mouse models, these animals display amyloid pathology but do not show neurofibrillary tangles or neuronal loss. This presumably is due to differences between the etiology of the aged-related human disease and the mouse models. Here we report the generation of two transgenic cynomolgus monkeys overexpressing the human gene for APP with Swedish, Artic, and Iberian mutations, and demonstrated expression of gene tagged green fluorescent protein marker in the placenta, amnion, hair follicles, and peripheral blood. We believe that these nonhuman primate models will be very useful to study the pathogenesis of dementia and AD. However, generated Tg monkeys still have some limitations. We employed the CAG promoter, which will promote gene expression in a non-tissue specific manner. Moreover, we used transgenic models but not knock-in models. Thus, the inserted transgene destroys endogenous gene(s) and may affect the phenotype(s). Nevertheless, it will be of great interest to determine whether these Tg monkeys will develop tauopathy and neurodegeneration similar to human AD. |
| Databáze: | OpenAIRE |
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