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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...

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Autores principales: Ijaz, Talha, Wakamiya, Maki, Sun, Hong, Recinos, Adrian, Tilton, Ronald G., Brasier, Allan R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
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.
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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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