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 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 RelACKO/CKOmice 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 RelACKO/CKOmice with Zp3-Cre transgenic led to embryonic lethality of RelA-deficient embryos. In contrast, mating of RelACKO/CKOmice 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 RelACKO/CKOmouse allows for efficient deletion of RelA in a tissue-specific manner. This RelACKO/CKOmouse will be an invaluable tool for deciphering the mechanistic roles of RelA in various cells and tissues during development and in disease.
Departments of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
Talha
T
Ijaz
Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA.
Maki
M
Wakamiya
Internal Medicine-Division of Endocrinology, University of Texas Medical Branch, Galveston, TX, USA.
Hong
H
Sun
Internal Medicine-Division of Endocrinology, University of Texas Medical Branch, Galveston, TX, USA.
Adrian
A
Recinos
Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA.|Internal Medicine-Division of Endocrinology, University of Texas Medical Branch, Galveston, TX, USA.|Sealy Center for Molecular Medicine, University of Texas Medical Branch, MRB 8.128, 301 University Blvd, Galveston, TX, 77555-1060, USA.
Ronald G
RG
Tilton
Departments of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA. arbrasie@utmb.edu.|Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA. arbrasie@utmb.edu.|Internal Medicine-Division of Endocrinology, University of Texas Medical Branch, Galveston, TX, USA. arbrasie@utmb.edu.|Sealy Center for Molecular Medicine, University of Texas Medical Branch, MRB 8.128, 301 University Blvd, Galveston, TX, 77555-1060, USA. arbrasie@utmb.edu.
Allan R
http://orcid.org/0000-0002-5012-4090
AR
Brasier
Col1a2; Cre; Flox; NF-kB; RelA; Tamoxifen; p65
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