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Production of transgenic pig as an Alzheimer’s disease model using a multi-cistronic vector system
Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with memory loss and cognitive impairments. An AD transgenic (Tg) pig model would be useful for preclinical testing of therapeutic agents. We generated an AD Tg pig by somatic cell nuclear transfer (SCNT) using a multi-ci...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460854/ https://www.ncbi.nlm.nih.gov/pubmed/28586343 http://dx.doi.org/10.1371/journal.pone.0177933 |
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author | Lee, Seung-Eun Hyun, Hyuk Park, Mi-Ryung Choi, Youngsok Son, Yeo-Jin Park, Yun-Gwi Jeong, Sang-Gi Shin, Min-Young Ha, Hee-Jin Hong, Hyun-Sok Choi, Min-Keyung Im, Gi-Sun Park, Eung-Woo Kim, Young-Ho Park, Chankyu Kim, Eun-Young Park, Se-Pill |
author_facet | Lee, Seung-Eun Hyun, Hyuk Park, Mi-Ryung Choi, Youngsok Son, Yeo-Jin Park, Yun-Gwi Jeong, Sang-Gi Shin, Min-Young Ha, Hee-Jin Hong, Hyun-Sok Choi, Min-Keyung Im, Gi-Sun Park, Eung-Woo Kim, Young-Ho Park, Chankyu Kim, Eun-Young Park, Se-Pill |
author_sort | Lee, Seung-Eun |
collection | PubMed |
description | Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with memory loss and cognitive impairments. An AD transgenic (Tg) pig model would be useful for preclinical testing of therapeutic agents. We generated an AD Tg pig by somatic cell nuclear transfer (SCNT) using a multi-cistronic vector that harbored three AD-related genes with a total of six well-characterized mutations: hAPP (K670N/M671L, I716V, and V717I), hTau (P301L), and hPS1 (M146V and L286P). Four AD Tg cell lines were established from Jeju black pig ear fibroblasts (JB-PEFs); the resultant JB-PEF(AD) cells harbored transgene integration, expressed transgene mRNAs, and had normal karyotypes. Tg line #2–1, which expressed high levels of the transgenes, was used for SCNT; cleavage and blastocyst rates of embryos derived from this line were lower than those of Non-Tg. These embryos yielded three piglets (Jeju National University AD-Tg pigs, JNUPIGs) revealed by microsatellite testing to be genetically identical to JB-PEF(AD). Transgenes were expressed in multiple tissues, and at especially high levels in brain, and Aβ-40/42, total Tau, and GFAP levels were high in brains of the Tg animals. Five or more copies of transgenes were inserted into chromosome X. This is the first report of an AD Tg pig derived from a multi-cistronic vector. |
format | Online Article Text |
id | pubmed-5460854 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-54608542017-06-15 Production of transgenic pig as an Alzheimer’s disease model using a multi-cistronic vector system Lee, Seung-Eun Hyun, Hyuk Park, Mi-Ryung Choi, Youngsok Son, Yeo-Jin Park, Yun-Gwi Jeong, Sang-Gi Shin, Min-Young Ha, Hee-Jin Hong, Hyun-Sok Choi, Min-Keyung Im, Gi-Sun Park, Eung-Woo Kim, Young-Ho Park, Chankyu Kim, Eun-Young Park, Se-Pill PLoS One Research Article Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with memory loss and cognitive impairments. An AD transgenic (Tg) pig model would be useful for preclinical testing of therapeutic agents. We generated an AD Tg pig by somatic cell nuclear transfer (SCNT) using a multi-cistronic vector that harbored three AD-related genes with a total of six well-characterized mutations: hAPP (K670N/M671L, I716V, and V717I), hTau (P301L), and hPS1 (M146V and L286P). Four AD Tg cell lines were established from Jeju black pig ear fibroblasts (JB-PEFs); the resultant JB-PEF(AD) cells harbored transgene integration, expressed transgene mRNAs, and had normal karyotypes. Tg line #2–1, which expressed high levels of the transgenes, was used for SCNT; cleavage and blastocyst rates of embryos derived from this line were lower than those of Non-Tg. These embryos yielded three piglets (Jeju National University AD-Tg pigs, JNUPIGs) revealed by microsatellite testing to be genetically identical to JB-PEF(AD). Transgenes were expressed in multiple tissues, and at especially high levels in brain, and Aβ-40/42, total Tau, and GFAP levels were high in brains of the Tg animals. Five or more copies of transgenes were inserted into chromosome X. This is the first report of an AD Tg pig derived from a multi-cistronic vector. Public Library of Science 2017-06-06 /pmc/articles/PMC5460854/ /pubmed/28586343 http://dx.doi.org/10.1371/journal.pone.0177933 Text en © 2017 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Lee, Seung-Eun Hyun, Hyuk Park, Mi-Ryung Choi, Youngsok Son, Yeo-Jin Park, Yun-Gwi Jeong, Sang-Gi Shin, Min-Young Ha, Hee-Jin Hong, Hyun-Sok Choi, Min-Keyung Im, Gi-Sun Park, Eung-Woo Kim, Young-Ho Park, Chankyu Kim, Eun-Young Park, Se-Pill Production of transgenic pig as an Alzheimer’s disease model using a multi-cistronic vector system |
title | Production of transgenic pig as an Alzheimer’s disease model using a multi-cistronic vector system |
title_full | Production of transgenic pig as an Alzheimer’s disease model using a multi-cistronic vector system |
title_fullStr | Production of transgenic pig as an Alzheimer’s disease model using a multi-cistronic vector system |
title_full_unstemmed | Production of transgenic pig as an Alzheimer’s disease model using a multi-cistronic vector system |
title_short | Production of transgenic pig as an Alzheimer’s disease model using a multi-cistronic vector system |
title_sort | production of transgenic pig as an alzheimer’s disease model using a multi-cistronic vector system |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460854/ https://www.ncbi.nlm.nih.gov/pubmed/28586343 http://dx.doi.org/10.1371/journal.pone.0177933 |
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