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Generation and characterization of a novel transgenic mouse harboring conditional nuclear factor-kappa B/RelA knockout alleles
BACKGROUND: Nuclear Factor-Kappa B (NF-kB) is a family of transcription factors that are important in embryonic development, inflammation, epithelial-to-mesenchymal transition and cancer. The 65 kDa RelA subunit is the major transcriptional activator of the NF-kB pathways. Whole-body deficiency of R...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034478/ https://www.ncbi.nlm.nih.gov/pubmed/27662828 http://dx.doi.org/10.1186/s12861-016-0135-8 |
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author | Ijaz, Talha Wakamiya, Maki Sun, Hong Recinos, Adrian Tilton, Ronald G. Brasier, Allan R. |
author_facet | Ijaz, Talha Wakamiya, Maki Sun, Hong Recinos, Adrian Tilton, Ronald G. Brasier, Allan R. |
author_sort | Ijaz, Talha |
collection | PubMed |
description | BACKGROUND: Nuclear Factor-Kappa B (NF-kB) is a family of transcription factors that are important in embryonic development, inflammation, epithelial-to-mesenchymal transition and cancer. The 65 kDa RelA subunit is the major transcriptional activator of the NF-kB pathways. Whole-body deficiency of RelA leads to massive apoptosis of liver hepatocytes and death in utero. To study the role of RelA in physiology and in disease states in a manner that circumvents this embryonic lethal phenotype, we have generated a mouse with RelA conditional knockout (CKO) alleles containing loxP sites that are deleted by activated Cre recombinase. RESULTS: We demonstrate that RelA(CKO/CKO) mice are fertile, do not display any developmental defects and can be crossed with Cre-expressing mice to delete RelA in a temporal, tissue-specific manner. Our mating of RelA(CKO/CKO) mice with Zp3-Cre transgenic led to embryonic lethality of RelA-deficient embryos. In contrast, mating of RelA(CKO/CKO) mice with Col1α2-CreER mice allowed for the generation of double transgenics which could be stimulated with tamoxifen to induce fibroblast-specific RelA deletion in adulthood. CONCLUSIONS: Based on our collective data, we conclude that this novel RelA(CKO/CKO) mouse allows for efficient deletion of RelA in a tissue-specific manner. This RelA(CKO/CKO) mouse will be an invaluable tool for deciphering the mechanistic roles of RelA in various cells and tissues during development and in disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12861-016-0135-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5034478 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50344782016-09-29 Generation and characterization of a novel transgenic mouse harboring conditional nuclear factor-kappa B/RelA knockout alleles Ijaz, Talha Wakamiya, Maki Sun, Hong Recinos, Adrian Tilton, Ronald G. Brasier, Allan R. BMC Dev Biol Methodology Article BACKGROUND: Nuclear Factor-Kappa B (NF-kB) is a family of transcription factors that are important in embryonic development, inflammation, epithelial-to-mesenchymal transition and cancer. The 65 kDa RelA subunit is the major transcriptional activator of the NF-kB pathways. Whole-body deficiency of RelA leads to massive apoptosis of liver hepatocytes and death in utero. To study the role of RelA in physiology and in disease states in a manner that circumvents this embryonic lethal phenotype, we have generated a mouse with RelA conditional knockout (CKO) alleles containing loxP sites that are deleted by activated Cre recombinase. RESULTS: We demonstrate that RelA(CKO/CKO) mice are fertile, do not display any developmental defects and can be crossed with Cre-expressing mice to delete RelA in a temporal, tissue-specific manner. Our mating of RelA(CKO/CKO) mice with Zp3-Cre transgenic led to embryonic lethality of RelA-deficient embryos. In contrast, mating of RelA(CKO/CKO) mice with Col1α2-CreER mice allowed for the generation of double transgenics which could be stimulated with tamoxifen to induce fibroblast-specific RelA deletion in adulthood. CONCLUSIONS: Based on our collective data, we conclude that this novel RelA(CKO/CKO) mouse allows for efficient deletion of RelA in a tissue-specific manner. This RelA(CKO/CKO) mouse will be an invaluable tool for deciphering the mechanistic roles of RelA in various cells and tissues during development and in disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12861-016-0135-8) contains supplementary material, which is available to authorized users. BioMed Central 2016-09-23 /pmc/articles/PMC5034478/ /pubmed/27662828 http://dx.doi.org/10.1186/s12861-016-0135-8 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Methodology Article Ijaz, Talha Wakamiya, Maki Sun, Hong Recinos, Adrian Tilton, Ronald G. Brasier, Allan R. Generation and characterization of a novel transgenic mouse harboring conditional nuclear factor-kappa B/RelA knockout alleles |
title | Generation and characterization of a novel transgenic mouse harboring conditional nuclear factor-kappa B/RelA knockout alleles |
title_full | Generation and characterization of a novel transgenic mouse harboring conditional nuclear factor-kappa B/RelA knockout alleles |
title_fullStr | Generation and characterization of a novel transgenic mouse harboring conditional nuclear factor-kappa B/RelA knockout alleles |
title_full_unstemmed | Generation and characterization of a novel transgenic mouse harboring conditional nuclear factor-kappa B/RelA knockout alleles |
title_short | Generation and characterization of a novel transgenic mouse harboring conditional nuclear factor-kappa B/RelA knockout alleles |
title_sort | generation and characterization of a novel transgenic mouse harboring conditional nuclear factor-kappa b/rela knockout alleles |
topic | Methodology Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034478/ https://www.ncbi.nlm.nih.gov/pubmed/27662828 http://dx.doi.org/10.1186/s12861-016-0135-8 |
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