Abstract
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/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 RelACKO/CKO mice with Zp3-Cre transgenic led to embryonic lethality of RelA-deficient embryos. In contrast, mating of RelACKO/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 RelACKO/CKO mouse allows for efficient deletion of RelA in a tissue-specific manner. This RelACKO/CKO mouse will be an invaluable tool for deciphering the mechanistic roles of RelA in various cells and tissues during development and in disease.
| Original language | English (US) |
|---|---|
| Article number | 32 |
| Journal | BMC Developmental Biology |
| Volume | 16 |
| Issue number | 1 |
| DOIs | |
| State | Published - Sep 23 2016 |
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Keywords
- Col1a2
- Cre
- Flox
- NF-kB
- p65
- RelA
- Tamoxifen
ASJC Scopus subject areas
- Developmental Biology
Cite this
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; Brasier, Allan R.
In: BMC Developmental Biology, Vol. 16, No. 1, 32, 23.09.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Generation and characterization of a novel transgenic mouse harboring conditional nuclear factor-kappa B/RelA knockout alleles
AU - Ijaz, Talha
AU - Wakamiya, Maki
AU - Sun, Hong
AU - Recinos, Adrian
AU - Tilton, Ronald
AU - Brasier, Allan R.
PY - 2016/9/23
Y1 - 2016/9/23
N2 - 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/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 RelACKO/CKO mice with Zp3-Cre transgenic led to embryonic lethality of RelA-deficient embryos. In contrast, mating of RelACKO/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 RelACKO/CKO mouse allows for efficient deletion of RelA in a tissue-specific manner. This RelACKO/CKO mouse will be an invaluable tool for deciphering the mechanistic roles of RelA in various cells and tissues during development and in disease.
AB - 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/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 RelACKO/CKO mice with Zp3-Cre transgenic led to embryonic lethality of RelA-deficient embryos. In contrast, mating of RelACKO/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 RelACKO/CKO mouse allows for efficient deletion of RelA in a tissue-specific manner. This RelACKO/CKO mouse will be an invaluable tool for deciphering the mechanistic roles of RelA in various cells and tissues during development and in disease.
KW - Col1a2
KW - Cre
KW - Flox
KW - NF-kB
KW - p65
KW - RelA
KW - Tamoxifen
UR - http://www.scopus.com/inward/record.url?scp=84992322890&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992322890&partnerID=8YFLogxK
U2 - 10.1186/s12861-016-0135-8
DO - 10.1186/s12861-016-0135-8
M3 - Article
AN - SCOPUS:84992322890
VL - 16
JO - BMC Developmental Biology
JF - BMC Developmental Biology
SN - 1471-213X
IS - 1
M1 - 32
ER -