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Transgene integration causes RARB downregulation in homozygous Tg4–42 mice
Alzheimer’s disease can be modelled by different transgenic mouse strains. To gain deeper insight into disease model mechanisms, the previously described Tg4–42 mouse was analysed for transgene integration. On RNA/DNA level the transgene integration resulted in more than 20 copy numbers and further...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156671/ https://www.ncbi.nlm.nih.gov/pubmed/32286473 http://dx.doi.org/10.1038/s41598-020-63512-8 |
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author | Hinteregger, Barbara Loeffler, Tina Flunkert, Stefanie Neddens, Joerg Birner-Gruenberger, Ruth Bayer, Thomas A. Madl, Tobias Hutter-Paier, Birgit |
author_facet | Hinteregger, Barbara Loeffler, Tina Flunkert, Stefanie Neddens, Joerg Birner-Gruenberger, Ruth Bayer, Thomas A. Madl, Tobias Hutter-Paier, Birgit |
author_sort | Hinteregger, Barbara |
collection | PubMed |
description | Alzheimer’s disease can be modelled by different transgenic mouse strains. To gain deeper insight into disease model mechanisms, the previously described Tg4–42 mouse was analysed for transgene integration. On RNA/DNA level the transgene integration resulted in more than 20 copy numbers and further caused a deletion of exon 2 of the retinoic acid receptor beta. These findings were also confirmed on protein level with highly decreased retinoic acid receptor beta protein levels in homozygous Tg4–42 mice and may have an impact on the previously described phenotype of homozygous Tg4–42 mice to be solely dependent on amyloid-ß 4–42 expression. Since hemizygous mice show no changes in RARB protein levels it can be concluded that the previously described phenotype of these mice should not be affected by the retinoic acid receptor beta gene knockout. In order to fully understand the results of transgenesis, it is extremely advisable to determine the genome integration site and the basic structure of the inserted transgenes. This can be carried out for instance by next-generation sequencing techniques. Our results thus suggest that a detailed characterization of new disease models using the latest genomics technologies prior to functional studies could be a valuable tool to avoid an unexpected genetic influence on the animals’ phenotype that is not only based on the inserted transgene. This would also significantly improve the selection of mouse models that are best suited for therapeutic development and basic research. |
format | Online Article Text |
id | pubmed-7156671 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-71566712020-04-19 Transgene integration causes RARB downregulation in homozygous Tg4–42 mice Hinteregger, Barbara Loeffler, Tina Flunkert, Stefanie Neddens, Joerg Birner-Gruenberger, Ruth Bayer, Thomas A. Madl, Tobias Hutter-Paier, Birgit Sci Rep Article Alzheimer’s disease can be modelled by different transgenic mouse strains. To gain deeper insight into disease model mechanisms, the previously described Tg4–42 mouse was analysed for transgene integration. On RNA/DNA level the transgene integration resulted in more than 20 copy numbers and further caused a deletion of exon 2 of the retinoic acid receptor beta. These findings were also confirmed on protein level with highly decreased retinoic acid receptor beta protein levels in homozygous Tg4–42 mice and may have an impact on the previously described phenotype of homozygous Tg4–42 mice to be solely dependent on amyloid-ß 4–42 expression. Since hemizygous mice show no changes in RARB protein levels it can be concluded that the previously described phenotype of these mice should not be affected by the retinoic acid receptor beta gene knockout. In order to fully understand the results of transgenesis, it is extremely advisable to determine the genome integration site and the basic structure of the inserted transgenes. This can be carried out for instance by next-generation sequencing techniques. Our results thus suggest that a detailed characterization of new disease models using the latest genomics technologies prior to functional studies could be a valuable tool to avoid an unexpected genetic influence on the animals’ phenotype that is not only based on the inserted transgene. This would also significantly improve the selection of mouse models that are best suited for therapeutic development and basic research. Nature Publishing Group UK 2020-04-14 /pmc/articles/PMC7156671/ /pubmed/32286473 http://dx.doi.org/10.1038/s41598-020-63512-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hinteregger, Barbara Loeffler, Tina Flunkert, Stefanie Neddens, Joerg Birner-Gruenberger, Ruth Bayer, Thomas A. Madl, Tobias Hutter-Paier, Birgit Transgene integration causes RARB downregulation in homozygous Tg4–42 mice |
title | Transgene integration causes RARB downregulation in homozygous Tg4–42 mice |
title_full | Transgene integration causes RARB downregulation in homozygous Tg4–42 mice |
title_fullStr | Transgene integration causes RARB downregulation in homozygous Tg4–42 mice |
title_full_unstemmed | Transgene integration causes RARB downregulation in homozygous Tg4–42 mice |
title_short | Transgene integration causes RARB downregulation in homozygous Tg4–42 mice |
title_sort | transgene integration causes rarb downregulation in homozygous tg4–42 mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156671/ https://www.ncbi.nlm.nih.gov/pubmed/32286473 http://dx.doi.org/10.1038/s41598-020-63512-8 |
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