RBRC01390, B6.129P2-Nfe2l2<tm1Mym>/MymRbrc

RBRC No. RBRC01390
Type Targeted MutationCartagena wks
Species Mus musculus
Strain name B6.129P2-Nfe2l2<tm1Mym>/MymRbrc
Former Common name Nrf2 knockout mouse/C57BL6J
H-2 Haplotype No Data
ES cell line E14 [129P2/OlaHsd]
Donor strain 129P2/OlaHsd via E14 ES cell line
Background strain C57BL/6
1 Appearance Black
Genotype a/a B/B C/C
Strain development Developed by Masayuki Yamamoto, Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba in 1996. The targeting vector containing lacZ-neo cassette was transferred into E14 ES cells to replace the 1.2 kb segment containing the rest of the exon 5 coding sequence of the Nrf2 gene.
Strain description Nrf2 (Nfe2l2) Knockout mice. This strain is a useful model for the in vivo analysis of chemical carcinogenesis and resistance to anti-cancer drugs. A phenolic antioxidant significantly induced the expression of phase II enzymes such as glutathione S-transferase and NAD(P)H: quinone oxidoreductase in normal mice. However, in the homozygous Nrf2 deficient mice the induction of the phase II enzymes by a phenolic antioxidant was largely eliminated in the liver and intestine. Since Nrf2 is constantly degraded by proteasome under normal condition, it is hardly to detect Nrf2 protein in the absence of stimuli. Electrophilic chemicals, such as DEM (diethyl maleate) and tBHQ (tert-buthyl hydroquinone), are generally used to stabilize Nrf2. Or proteasomal inhibitors, such as MG132, are also effective increasing the protein amount of Nrf2. C57BL/6 background (RBRC01390), BALB/c background (RBRC02190), A/J background (RBRC02414), ICR mixed background (RBRC00984). Homozygous mutant mice are viable and fertile, but show lower reproductive performance.
Colony maintenance Homozygote x Heterozygote [or Crossing to C57BL/6JJcl]
Health Report
Gene Details
Promoter No Data
1 Symbol Nfe2l2
Symbol name nuclear factor, erythroid derived 2, like 2
Chromosome 2
Common name Nrf2
Symbol description No Data
2 Symbol lacZ
Symbol name beta-galactosidase (E. coli)
Chromosome 2
Common name No Data
Symbol description E. coli beta galactosidase
3 Symbol nls
Symbol name SV40 large T antigen nuclear localization signal (NLS)
Chromosome 2
Common name No Data
Symbol description No Data
Promoter herpes simplex virus thymidine kinase promoter (HSV tk promoter)
4 Symbol neo
Symbol name neomycin resistance gene (E. coli)
Chromosome 2
Common name neo; neomycin;
Symbol description No Data
References Biochem Biophys Res Commun. 1997 Jul 18;236(2):313-22.

Induction of sulfiredoxin via an Nrf2-dependent pathway and hyperoxidation of peroxiredoxin III in the lungs of mice exposed to hyperoxia.
Induction of sulfiredoxin via an Nrf2-dependent pathway and hyperoxidation of peroxiredoxin III in the lungs of mice exposed to hyperoxia.
Research applications Fluorescent Proteins/lacZ System
Specific Term and Conditions The following terms and conditions will be requested by the DEPOSITOR.
The RECIPIENT of BIOLOGICAL RESOURCE shall obtain a prior written consent on use of it from the DEPOSITOR.
In publishing the research results obtained by use of the BIOLOGICAL RESOURCE, a citation of the following literature(s) designated by the DEPOSITOR is requested.
Biochem. Biophys. Res. Commun., 236, 313-322 (1997).
The RECIPIENT agrees that it will acknowledge the DEPOSITOR as academically and scientifically appropriate in its articles when the Recipient publishes its data using these mice. Recipient should contact the DEPOSITOR in the case of application for any patents with the results from these mice.
Additional information
1 Mouse of the Month Oct 2005
Mouse of the Month Apr 2012
Genetic Background
Breeding characters
2 Lab HP (Japanese)
3 Genotyping protocol <PCR>
Depositor Yamamoto, Masayuki (University of tsukuba) Yamamoto, Masayuki
Strain Status /
(Expected delivery)

Cryopreserved embryos : Within 1 month
Recovered litters from cryopreserved embryos : 2-4 months

Cryopreserved sperm : Within 1 month
Recovered litters from cryopreserved sperm : 2-4 months

Live mouse :
BRC mice in Publications
Title Journal
Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages. Mol Immunol.45(7): 2106-15 (2008).(18022235)
Ashino T, Yamanaka R, Yamamoto M, Shimokawa H, Sekikawa K, Iwakura Y, Shioda S, Numazawa S, Yoshida T.
Induction of sulfiredoxin via an Nrf2-dependent pathway and hyperoxidation of peroxiredoxin III in the lungs of mice exposed to hyperoxia. Antioxid Redox Signal.11(5): 937-948 (2009).(19086807)
Bae SH, Woo HA, Sung SH, Lee HE, Lee SK, Kil IS, Rhee SG.
TLR2-dependent inhibition of macrophage responses to IFN-gamma is mediated by distinct, gene-specific mechanisms. PLoS One.4(7): e6329 (2009).(19629181)
Benson SA, Ernst JD.
Activation of Nrf2 in endothelial cells protects arteries from exhibiting a proinflammatory state. Arterioscler Thromb Vasc Biol.29(11): 1851-7 (2009).(19729611)
Zakkar M, Van der Heiden K, Luong le A, Chaudhury H, Cuhlmann S, Hamdulay SS, Krams R, Edirisinghe I, Rahman I, Carlsen H, Haskard DO, Mason JC, Evans PC.
Protection of vascular cells from oxidative stress by proteasome inhibition depends on Nrf2. Cardiovasc Res.85(2): 395-403 (2010).(19679681)
Dreger H, Westphal K, Wilck N, Baumann G, Stangl V, Stangl K, Meiners S.
NF-E2-related factor 2 regulates the stress response to UVA-1-oxidized phospholipids in skin cells. FASEB J.24(1): 39-48 (2010).(19720622)
Gruber F, Mayer H, Lengauer B, Mlitz V, Sanders JM, Kadl A, Bilban M, de Martin R, Wagner O, Kensler TW, Yamamoto M, Leitinger N, Tschachler E.
Induction of heme oxygenase-1 in normal and malignant B lymphocytes by 15-deoxy-Delta(12,14)-prostaglandin J(2) requires Nrf2. Cell Immunol.262(1): 18-27 (2010).(20064636)
Bancos S, Baglole CJ, Rahman I, Phipps RP.
Simvastatin lowers reactive oxygen species level by Nrf2 activation via PI3K/Akt pathway. Biochem Biophys Res Commun.396(2): 463-6 (2010).(20417615)
Chartoumpekis D, Ziros PG, Psyrogiannis A, Kyriazopoulou V, Papavassiliou AG, Habeos IG.
Redox regulation of lipopolysaccharide-mediated sulfiredoxin induction, which depends on both AP-1 and Nrf2. J Biol Chem.285(45): 34419-28 (2010).(20826812)
Kim H, Jung Y, Shin BS, Kim H, Song H, Bae SH, Rhee SG, Jeong W.
Nrf2 deficiency influences susceptibility to steroid resistance via HDAC2 reduction. Biochem Biophys Res Commun.403(3-4): 452-6 (2010).(21094147)
Adenuga D, Caito S, Yao H, Sundar IK, Hwang JW, Chung S, Rahman I.
Concerted action of sulfiredoxin and peroxiredoxin I protects against alcohol-induced oxidative injury in mouse liver. Hepatology.53(3): 945-53 (2011).(21319188)
Bae SH, Sung SH, Cho EJ, Lee SK, Lee HE, Woo HA, Yu DY, Kil IS, Rhee SG.
Nitric oxide activates an Nrf2/sulfiredoxin antioxidant pathway in macrophages. Free Radic Biol Med. (2011).(21466852)
Abbas K, Breton J, Planson AG, Bouton C, Bignon J, Seguin C, Riquier S, Toledano MB, Drapier JC.
Nrf2 is essential for cholesterol crystal-induced inflammasome activation and exacerbation of atherosclerosis. Eur J Immunol. (2011).(21484785)
Freigang S, Ampenberger F, Spohn G, Heer S, Shamshiev AT, Kisielow J, Hersberger M, Yamamoto M, Bachmann MF, Kopf M.
Nrf2 inhibits LXRalpha-dependent hepatic lipogenesis by competing with FXR for acetylase binding. Antioxid Redox Signal. (2011).(21504366)
Kay HY, Kim WD, Hwang SJ, Choi HS, Gilroy RK, Wan YJ, Kim SG.
Nrf2 Represses FGF21 During Long-Term High-Fat Diet-Induced Obesity in Mice. Diabetes. (2011).(21852674)
Chartoumpekis DV, Ziros PG, Psyrogiannis AI, Papavassiliou AG, Kyriazopoulou VE, Sykiotis GP, Habeos IG.
Extract of the mushroom Mycoleptodonoides aitchisonii induces a series of anti-oxidative and phase II detoxifying enzymes through activation of the transcription factor Nrf2. Food Chemistry129(1): 92-99 (2011).
Kokubo T, Taniguchi Y, Kanayama M, Shimura M, Konishi Y, Kawagishi H, Yamamoto M, Shindo K and Yoshida A.
Loss of Transcription Factor Nuclear Factor-Erythroid 2 (NF-E2) p45-related Factor-2 (Nrf2) Leads to Dysregulation of Immune Functions, Redox Homeostasis, and Intracellular Signaling in Dendritic Cells. J Biol Chem.287(13): 10556-64 (2012).(22311972)
Yeang HX, Hamdam JM, Al-Huseini LM, Sethu S, Djouhri L, Walsh J, Kitteringham N, Park BK, Goldring CE, Sathish JG.
Bryonolic Acid Transcriptional Control of Anti-inflammatory and Antioxidant Genes in Macrophages in Vitro and in Vivo. J Nat Prod. (2012).(22339499)
Gatbonton-Schwager TN, Letterio JJ, Tochtrop GP.
Oxidative stress fuels Trypanosoma cruzi infection in mice. J Clin Invest.122(7): 2531-42 (2012).(22728935)
Paiva CN, Feij DF, Dutra FF, Carneiro VC, Freitas GB, Alves LS, Mesquita J, Fortes GB, Figueiredo RT, Souza HS, Fantappi MR, Lannes-Vieira J, Bozza MT.
Nrf2 promotes alveolar mitochondrial biogenesis and resolution of lung injury in Staphylococcus aureus pneumonia in mice. Free Radic Biol Med.53(8): 1584-94 (2012).(22940620)
Athale J, Ulrich A, Chou Macgarvey N, Bartz RR, Welty-Wolf KE, Suliman HB, Piantadosi CA.
Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. Cell Metab.17(1): 73-84 (2013).(23274085)
Bae SH, Sung SH, Oh SY, Lim JM, Lee SK, Park YN, Lee HE, Kang D, Rhee SG.
The microglial alpha 7 acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing HO-1 via Nrf2. Antioxid Redox Signal. (2013).(23311871)
Parada E, Egea J, Buendia I, Negredo P, Cunha AC, Cardoso S, Soares MP, Lopez MG.
Allergic Skin Inflammation Induced by Chemical Sensitizers Is Controlled by the Transcription Factor Nrf2. Toxicol Sci. (2013).(23564646)
El Ali Z, Gerbeix C, Hemon P, Esser PR, Martin SF, Pallardy M, Kerdine-R mer S.
The Role of Tumor Necrosis Factor-alpha and Interferon-gamma in Regulating Angiomotin-Like Protein 1 Expression in Lung Microvascular Endothelial Cells. Allergol Int. (2013).(23793505)
Nakajima Y, Nakamura Y, Shigeeda W, Tomoyasu M, Deguchi H, Tanita T, Yamauchi K.
SIRT1 protects against cigarette smoke-induced lung oxidative stress via a FOXO3-dependent mechanism. Am J Physiol Lung Cell Mol Physiol.306(9) : L816-28 (2014).(24633890)
Yao H, Sundar IK, Ahmad T, Lerner C, Gerloff J, Friedman AE, Phipps RP, Sime PJ, McBurney MW, Guarente L, Rahman I.
Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52. Nat Commun.5: 3496 (2014).(24667209)
Jo C, Gundemir S, Pritchard S, Jin YN, Rahman I, Johnson GV.
Control of disease tolerance to malaria by nitric oxide and carbon monoxide. Cell Rep.8(1) : 126-36 (2014).(24981859)
Jeney V, Ramos S, Bergman ML, Bechmann I, Tischer J, Ferreira A, Oliveira-Marques V, Janse CJ, Rebelo S, Cardoso S, Soares MP.
Phospholipid oxidation generates potent anti-inflammatory lipid mediators that mimic structurally related pro-resolving eicosanoids by activating Nrf2. EMBO Mol Med7(5): 593-607 (2015).(25770125)
Bretscher P, Egger J, Shamshiev A, Trötzmüller M, Köfeler H, Carreira EM, Kopf M, Freigang S.
Identifying panaxynol, a natural activator of nuclear factor erythroid-2 related factor 2 (Nrf2) from American ginseng as a suppressor of inflamed macrophage-induced cardiomyocyte hypertrophy. J Ethnopharmacol168: 326-36 (2015).(25882312)
Qu C, Li B, Lai Y, Li H, Windust A, Hofseth LJ, Nagarkatti M, Nagarkatti P, Wang XL, Tang D, Janicki JS, Tian X, Cui T.
Nrf2-signaling and BDNF: A new target for the antidepressant-like activity of chronic fluoxetine treatment in a mouse model of anxiety/depression. Neurosci. Lett. (2015).(25916883)
Mendez-David I, Tritschler L, Ali ZE, Damiens MH, Pallardy M, David DJ, Kerdine-Röer S, Gardier AM.
Iron gene expression profile in atherogenic Mox macrophages. Biochim. Biophys. Acta. (2016).(26972048)
Marques L, Negre-Salvayre A, Costa L, Canonne-Hergaux F.
Mitigation of tight junction protein dysfunction in lung microvascular endothelial cells with pitavastatin. Pulm Pharmacol Ther. (2016).(27179426)
Suzuki R, Nakamura Y, Chiba S, Mizuno T, Abe K, Horii Y, Nagashima H, Tanita T, Yamauchi K.
Bacteroides fragilis Enterotoxin Upregulates Heme Oxygenase-1 in Intestinal Epithelial Cells via a Mitogen-Activated Protein Kinases- and NF-κB-Dependent Pathway, Leading to Modulation of Apoptosis. Infect. Immun.84(7): (2016).(27324483)
Su Hyuk Ko, Da Jeong Rho, Jong Ik Jeon, Young-Jeon Kim, Hyun Ae Woo, Yun Kyung Lee and Jung Mogg Kim.
Nuclear Factor (Erythroid-Derived)-Related Factor 2-Associated Retinal Pigment Epithelial Cell Protection under Blue Light-Induced Oxidative Stress. Oxid. Med. Cell. Longev. (2016).(27774118)
Takayama K, Kaneko H, Kataoka K, Kimoto R, Hwang SJ, Ye F, Nagasaka Y, Tsunekawa T, Matsuura T, Nonobe N, Ito Y, Terasaki H.
Effects of deficiency of Kelch-like ECH-associated protein 1 on skeletal organization: a mechanism for diminished nuclear factor of activated T cells cytoplasmic 1 during osteoclastogenesis. FASEB J.31(9): 4011-4022 (2017).(28515152)
Sakai E, Morita M, Ohuchi M, Kido MA, Fukuma Y, Nishishita K, Okamoto K, Itoh K, Yamamoto M, Tsukuba T.
Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis. Sci Rep7(1): 5812 (2017).(28724916)
Santarino IB, Viegas MS, Domingues NS, Ribeiro AM, Soares MP, Vieira OV.
Licochalcone A activates Keap1-Nrf2 signaling to suppresses arthritis via phosphorylation of p62 at serine 349. Free Radic. Biol. Med. (2017).(29233793)
Su X, Li T, Liu Z, Huang Q, Liao K, Ren R, Lu L, Qi X, Wang M, Chen J, Zhou H, Leung EL, Pan H, Liu J, Wang H, Huang L, Liu L.
Nrf2 mediates the expression of BAG3 and autophagy cargo adaptor proteins and tau clearance in an age dependent manner. Neurobiol. Aging. (2018).(29304346)
Maoping Tang, Changyi Ji, Susanne Pallo, Irfan Rahman, Gail V.W. Johnson.
Implication of basal lamina dependency in survival of Nrf2-null muscle stem cells via an antioxidative-independent mechanism. J. Cell Physiol. (2018).(30070693)
Takemoto Y, Inaba S, Zhang L, Tsujikawa K, Uezumi A, Fukada SI.
Astragali radix and its main bioactive compounds activate the Nrf2-mediated signaling pathway to induce P-glycoprotein and breast cancer resistance protein. J. Ethnopharmacol.228: 82-91 (2018).(30243825)
Lou Y, Guo Z, Zhu Y, Zhang G, Wang Y, Qi X, Lu L, Liu Z, Wu J.