Complexity of CNC Transcription Factors As Revealed by Gene Targeting of the Nrf3 Locus
Open accessAbstract
Cap'n'collar (CNC) family basic leucine zipper transcription factors play crucial roles in the regulation of mammalian gene expression and development. To determine the in vivo function of the CNC protein Nrf3 (NF-E2-related factor 3), we generated mice deficient in this transcription factor. We performed targeted disruption of two Nrf3 exons coding for CNC homology, basic DNA-binding, and leucine zipper dimerization domains. Nrf3 null mice developed normally and revealed no obvious phenotypic differences compared to wild-type animals. Nrf3(-/-) mice were fertile, and gross anatomy as well as behavior appeared normal. The mice showed normal age progression and did not show any apparent additional phenotype during their life span. We observed no differences in various blood parameters and chemistry values. We infected wild-type and Nrf3(-/-) mice with acute lymphocytic choriomeningitis virus and found no differences in these animals with respect to their number of virus-specific CD8 and CD4 T cells as well as their B-lymphocyte response. To determine whether the mild phenotype of Nrf3 null animals is due to functional redundancy, we generated mice deficient in multiple CNC factors. Contrary to our expectations, an absence of Nrf3 does not seem to cause additional lethality in compound Nrf3(-/-)/Nrf2(-/-) and Nrf3(-/-)/p45(-/-) mice. We hypothesize that the role of Nrf3 in vivo may become apparent only after appropriate challenge to the mice.
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Nrf3-deficient mice display no overt signs of any abnormalities under physiological conditions.
“However, the biological function of Nrf3 is less clear since Nrf3-deficient mice display no overt signs of any abnormalities under physiological conditions.25”
From Novel roles of Nrf3–Trim5 axis in vascular smooth muscle cell dysfunctions and neointimal hyperplasia (2025) · cites this paper as [25]
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References 64 · Cited by 100
Research works printed but not linked: 1
- [3]Andrews, N. C. 1998. The NF-E2 transcription factor. Int. J. Biochem. Cell Biol. 30:429-432. [DOI] [PubMed] [Google Scholar]
- Authors
- Derjuga, A., Gourley, T. S., Holm, T. M., Heng, H. H. Q., Shivdasani, R. A., Ahmed, R., Andrews, N. C., & Blank, V.
- Affiliations
- Lady Davis Institute for Medical Research (CA)
- Emory University (US)
- Division of Hematology/Oncology, Children's Hospital
- Wayne State University (US)
- Dana-Farber Cancer Institute (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Blank, Volker
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-04
- Volume
- 24
- Issue
- 8
- Pages
- 3286-3294
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC381672
- OpenAlex
- W2098215375
- Cited by
- 100
- References
- 64
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 7 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 4 · 2014: 2 · 2013: 5 · 2012: 3
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Leukemia and Lymphoma Society
- Cancer Research Society
- Israel National Institute for Health Policy Research
- National Institutes of Health (n01ai30048-10-0-1)
- Canadian Institutes of Health Research
- National Heart, Lung, and Blood Institute (HL 63143, R01HL063143, R01HL051057, R56HL063143, HL51057)
- National Institute of Allergy and Infectious Diseases (N01 AI030048, AI 30048)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH-P30-HD-18655, P30HD018655)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- Nrf3, bZIP transcription factors, functional redundancy, Nrf2, P45, lymphocytic choriomeningitis virus, T cell response, B cell response, age progression
- MeSH terms
- Animals, Arenaviridae Infections, Chromosomes, DNA-Binding Proteins, Exons, Female, Fetal Viability, Lymphocytic choriomeningitis virus, Male, Phenotype, Repressor Proteins, Tissue Distribution, Transcription Factors, Trans-Activators, Leucine Zippers, In Situ Hybridization, Fluorescence, Mice, Knockout, Gene Targeting, Basic-Leucine Zipper Transcription Factors, Erythroid-Specific DNA-Binding Factors, NF-E2 Transcription Factor, NF-E2 Transcription Factor, p45 Subunit, NF-E2-Related Factor 2, Mice
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