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October 2005 Mouse of the Month |
Nrf2 & Keap1
Key Molecules for Defense against Physiological Stress |
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| Targeted mutation | |
| Gene Symbol: Nfe2l2, nuclear factor, erythroid derived 2, like 2 (OMIM600492) | |
| BRC No. 00984 Nrf2 knock out mouse (ICR/129Sv background) | |
| BRC No. 01390 Nrf2 knock out mouse (C57BL/6 background) | |
| Targeted mutation | |
| Gene Symbol: Keap1, kelch-like ECH-associated protein 1 (OMIM606016) | |
| BRC No. 01388 Keap1 knock out mouse | |
Research Application: Apoptosis; Cell Cycle; Cancer; Immunology and Inflammation; Aging; DNA repair Mechanism; Toxicology
The Nrf2-deficient and Keap1-deficient mouse strains were created by homologous recombination with E14 ES cells derived from 129P2/OlaHsd. The transcription factor Nrf2 regulates the expression of a series of detoxifying and antioxidant genes. A phenolic antioxidant in vivo significantly induced the expression of phase II detoxifying enzymes in wild-type mice as defense against intake of xenobiotics. This defense mechanism with induction of phase II enzymes was eliminated in the Nrf2-deficient mice. The cytoplasmic protein Keap1 interacts with Nrf2, acts as a negative regulator of Nrf2 and as a sensor of xenobiotic and oxidative stresses. Double knockout mice of Nrf2 and Keap1 demonstrated that Nrf2 is a primary target of Keap1. Nrf2-Keap1 system is one of the major cellular protection mechanisms against xenobiotic and oxidative stresses.
The Nrf2-deficient and Keap1-deficient mouse strains were created by homologous recombination with E14 ES cells derived from 129P2/OlaHsd. The transcription factor Nrf2 regulates the expression of a series of detoxifying and antioxidant genes. A phenolic antioxidant in vivo significantly induced the expression of phase II detoxifying enzymes in wild-type mice as defense against intake of xenobiotics. This defense mechanism with induction of phase II enzymes was eliminated in the Nrf2-deficient mice. The cytoplasmic protein Keap1 interacts with Nrf2, acts as a negative regulator of Nrf2 and as a sensor of xenobiotic and oxidative stresses. Double knockout mice of Nrf2 and Keap1 demonstrated that Nrf2 is a primary target of Keap1. Nrf2-Keap1 system is one of the major cellular protection mechanisms against xenobiotic and oxidative stresses.
| Depositor | : | Dr. Masayuki Yamamoto |
| References | : | Trends Mol Med. 10, 549-557 (2004). Nat Genet. 35, 238-245 (2003). Biochem. Biophys. Res. Commun., 236, 313-322 (1997). |
