Nrf2 & Keap1

RIKEN BRC October 2005
Mouse of the Month
Nrf2 & Keap1

Key Molecules for Defense against Physiological Stress
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
mn051027_0101 mn051027_0102


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.


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).

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