Strain Information | |
---|---|
Image | |
BRC No. | RBRC01390 |
Type | Targeted Mutation |
Species | Mus musculus |
Strain name | B6.129P2-Nfe2l2<tm1Mym>/MymRbrc |
Former Common name | Nrf2 knockout mouse/C57BL6J |
H-2 Haplotype | |
ES Cell line | E14 [129P2/OlaHsd] |
Background strain | C57BL/6 |
Appearance | Black [a/a B/B C/C] |
Strain development | 筑波大学先端学際領域研究センター・山本雅之先生(1996)。 |
Strain description | Nrf2 (Nfe2l2) 遺伝子のノックアウトマウス。Nrf2は生体防御システムの遺伝子群の発現を活性化させる転写因子として知られている。活性酸素種、親電子性物質、重金属などの生体異物にさらされると、それらの毒性を排除するために解毒化酵素や酸化ストレス応答蛋白質が転写誘導される。Nrf2はそれらの転写の発現を誘導している。Nrf2ノックアウトマウスでは、抗酸化剤応答配列を介した遺伝子発現が減弱しており、親電子物質に対して感受性が高くなっている。また、親電子性物質が遺伝子点変異を誘起することから、Nrf2遺伝子が発ガンや動脈硬化、脳神経障害の予防に役立つ可能性も期待されている。C57BL/6背景 (RBRC01390) 、BALB/c背景 (RBRC02190) 、A/J背景 (RBRC02414) 、ICR混合背景 (RBRC00984) 。ホモマウスは生存性、繁殖性はあるものの、繁殖効率は低くなる。 |
Colony maintenance | Homozygote x Heterozygote [or Crossing to C57BL/6JJcl] |
References | Biochem. Biophys. Res. Commun., 236, 313-322, (1997) 9240432 |
Health Report | |
---|---|
Examination Date / Room / Rack | 2024/03/11Room:3-6Rack:D 2023/12/11Room:3-6Rack:D 2023/09/22Room:3-6Rack:D 2023/09/11Room:3-6Rack:D 2023/06/13Room:3-6Rack:D 2023/03/13Room:3-6Rack:D 2022/12/12Room:3-6Rack:D 2022/09/12Room:3-6Rack:D 2022/06/13Room:3-6Rack:D |
Gene | |
---|---|
Gene info | Gene symbolGene nameChr.Allele symbolAllele nameCommon namesPromoter Nfe2l2nuclear factor, erythroid derived 2, like 22Nfe2l2<tm1Mym>targeted mutation 1, Masayuki YamamotoNrf2 Gene symbolGene nameChr.Allele symbolAllele nameCommon namesPromoter lacZbeta-galactosidase (E. coli)2 Gene symbolGene nameChr.Allele symbolAllele nameCommon namesPromoter neoneomycin resistance gene (E. coli)2neo; neomycin;herpes simplex virus thymidine kinase promoter (HSV tk promoter) Gene symbolGene nameChr.Allele symbolAllele nameCommon namesPromoter nlsSV40 large T antigen nuclear localization signal (NLS)2nls |
Ordering Information | |
---|---|
供与核酸 | Simian virus 40 Large T antigen nuclear localization signal (NLS), E. coli lacZ, herpes simplex virus thymidine kinase promoter (HSV tk promoter), E. coli neo, mouse Nrf2 genomic DNA |
Research application | Fluorescent Proteins/lacZ System |
提供条件 | 条件を付加する。利用者は事前に寄託者の提供承諾書を得る。 研究成果の公表にあたって寄託者の指定する文献を引用する。Biochem. Biophys. Res. Commun., 236, 313-322 (1997). 当該リソースを使用した研究結果に基づき特許等の申請を行う場合は、寄託者と別途協議を行う。 |
Depositor | 山本 雅之(国立大学法人筑波大学) |
Strain Status | 生体 凍結胚 凍結精子 |
Strain Availability | 凍結精子を1ヶ月以内に提供可能 凍結胚を1ヶ月以内に提供可能 生体マウスを1~3ヶ月以内に提供可能 |
Additional Info. | Necessary documents for ordering:
Genotyping protocol -PCR- Genetic Background Breeding characters Mouse of the Month Oct 2005 Mouse of the Month Apr 2012 |
BRC mice in Publications |
---|
Nakajima Y, Nakamura Y, Shigeeda W, Tomoyasu M, Deguchi H, Tanita T, Yamauchi K. The role of tumor necrosis factor-α and interferon-γ in regulating angiomotin-like protein 1 expression in lung microvascular endothelial cells. Allergol Int 62(3) 309-22(2013) 23793505 Yao H, Sundar IK, Ahmad T, Lerner C, Gerloff J, Friedman AE, Phipps RP, Sime PJ, McBurney MW, Guarente L, Rahman I. 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 Parada E, Egea J, Buendia I, Negredo P, Cunha AC, Cardoso S, Soares MP, López MG. The microglial α7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2. Antioxid Redox Signal 19(11) 1135-48(2013) 23311871 Kay HY, Kim WD, Hwang SJ, Choi HS, Gilroy RK, Wan YJ, Kim SG. Nrf2 inhibits LXRα-dependent hepatic lipogenesis by competing with FXR for acetylase binding. Antioxid Redox Signal 15(8) 2135-46(2011) 21504366 Bae SH, Woo HA, Sung SH, Lee HE, Lee SK, Kil IS, Rhee SG. 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) 937-48(2009) 19086807 Fotini Filippopoulou, George I. Habeos, Vagelis Rinotas, Antonia Sophocleous, Gerasimos P. Sykiotis, Eleni Douni, Dionysios V. Chartoumpekis Dexamethasone Administration in Mice Leads to Less Body Weight Gain over Time, Lower Serum Glucose, and Higher Insulin Levels Independently of NRF2 Antioxidants 11 4(2021) 35052508 Habeos GI, Filippopoulou F, Habeos EE, Kalaitzopoulou E, Skipitari M, Papadea P, Lagoumintzis G, Niarchos A, Georgiou CD, Chartoumpekis DV. Maternal Calorie Restriction Induces a Transcriptional Cytoprotective Response in Embryonic Liver Partially Dependent on Nrf2. Antioxidants (Basel) 11(11) (2022) 36421460 Takagi T, Naito Y, Mizushima K, Hirai Y, Kamada K, Uchiyama K, Handa O, Ishikawa T, Itoh Y. 15-Deoxy-Δ12,14-prostaglandin J2 ameliorates dextran sulfate sodium-induced colitis in mice through heme oxygenase-1 induction. Arch Biochem Biophys 677 108183(2019) 31704099 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. Activation of Nrf2 in endothelial cells protects arteries from exhibiting a proinflammatory state. Arterioscler Thromb Vasc Biol 29(11) 1851-7(2009) 19729611 Adenuga D, Caito S, Yao H, Sundar IK, Hwang JW, Chung S, Rahman I. Nrf2 deficiency influences susceptibility to steroid resistance via HDAC2 reduction. Biochem Biophys Res Commun 403(3-4) 452-6(2010) 21094147 Chartoumpekis D, Ziros PG, Psyrogiannis A, Kyriazopoulou V, Papavassiliou AG, Habeos IG. Simvastatin lowers reactive oxygen species level by Nrf2 activation via PI3K/Akt pathway. Biochem Biophys Res Commun 396(2) 463-6(2010) 20417615 Marques L, Negre-Salvayre A, Costa L, Canonne-Hergaux F. Iron gene expression profile in atherogenic Mox macrophages. Biochim Biophys Acta 1862(6) 1137-46(2016) 26972048 Liao K, Su X, Lei K, Liu Z, Lu L, Wu Q, Pan H, Huang Q, Zhao Y, Wang M, Cai J, Liu L, Li T. Sinomenine protects bone from destruction to ameliorate arthritis via activating p62Thr269/Ser272-Keap1-Nrf2 feedback loop. Biomed Pharmacother 135 111195(2021) 33395605 Li YJ, Shimizu T, Shinkai Y, Ihara T, Sugamata M, Kato K, Kobayashi M, Hirata Y, Inagaki H, Uzuki M, Akimoto T, Umezawa M, Takeda K, Azuma A, Yamamoto M, Kawada T. Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice. Biomedicines 8(10) (2020) 33096811 Dreger H, Westphal K, Wilck N, Baumann G, Stangl V, Stangl K, Meiners S. Protection of vascular cells from oxidative stress by proteasome inhibition depends on Nrf2. Cardiovasc Res 85(2) 395-403(2010) 19679681 Bancos S, Baglole CJ, Rahman I, Phipps RP. 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 Bae SH, Sung SH, Oh SY, Lim JM, Lee SK, Park YN, Lee HE, Kang D, Rhee SG. Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. Cell Metab 17(1) 73-84(2013) 23274085 Jeney V, Ramos S, Bergman ML, Bechmann I, Tischer J, Ferreira A, Oliveira-Marques V, Janse CJ, Rebelo S, Cardoso S, Soares MP. Control of disease tolerance to malaria by nitric oxide and carbon monoxide. Cell Rep 8(1) 126-36(2014) 24981859 Chartoumpekis DV, Ziros PG, Psyrogiannis AI, Papavassiliou AG, Kyriazopoulou VE, Sykiotis GP, Habeos IG. Nrf2 represses FGF21 during long-term high-fat diet-induced obesity in mice. Diabetes 60(10) 2465-73(2011) 21852674 Bretscher P, Egger J, Shamshiev A, Trötzmüller M, Köfeler H, Carreira EM, Kopf M, Freigang S. Phospholipid oxidation generates potent anti-inflammatory lipid mediators that mimic structurally related pro-resolving eicosanoids by activating Nrf2. EMBO Mol Med 7(5) 593-607(2015) 25770125 Alharthy SA, Hardej D. The role of transcription factor Nrf2 in the toxicity of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in C57BL/6 mouse astrocytes. Environ Toxicol Pharmacol 86 103652(2021) 33812015 Freigang S, Ampenberger F, Spohn G, Heer S, Shamshiev AT, Kisielow J, Hersberger M, Yamamoto M, Bachmann MF, Kopf M. Nrf2 is essential for cholesterol crystal-induced inflammasome activation and exacerbation of atherosclerosis. Eur J Immunol 41(7) 2040-51(2011) 21484785 Kim A, Koo JH, Lee JM, Joo MS, Kim TH, Kim H, Jun DW, Kim SG. NRF2-mediated SIRT3 induction protects hepatocytes from ER stress-induced liver injury. FASEB J 36(3) e22170(2022) 35104011 Sakai E, Morita M, Ohuchi M, Kido MA, Fukuma Y, Nishishita K, Okamoto K, Itoh K, Yamamoto M, Tsukuba T. 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 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. 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 Kokubo T, Taniguchi Y, Kanayama M, Shimura M, Konishi Y, Kawagishi H, Yamamoto M, Shindo K and Yoshida A. 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 Chemistry 129(1) 92-99(2011) 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. Licochalcone A activates Keap1-Nrf2 signaling to suppress arthritis via phosphorylation of p62 at serine 349. Free Radic Biol Med 115 471-483(2018) 29233793 Athale J, Ulrich A, MacGarvey NC, Bartz RR, Welty-Wolf KE, Suliman HB, Piantadosi CA. 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 Abbas K, Breton J, Planson AG, Bouton C, Bignon J, Seguin C, Riquier S, Toledano MB, Drapier JC. Nitric oxide activates an Nrf2/sulfiredoxin antioxidant pathway in macrophages. Free Radic Biol Med 51(1) 107-14(2011) 21466852 Bae SH, Sung SH, Cho EJ, Lee SK, Lee HE, Woo HA, Yu DY, Kil IS, Rhee SG. Concerted action of sulfiredoxin and peroxiredoxin I protects against alcohol-induced oxidative injury in mouse liver. Hepatology 53(3) 945-53(2011) 21319188 Ko SH, Rho da J, Jeon JI, Kim YJ, Woo HA, Lee YK, Kim JM. Bacteroides fragilis Enterotoxin Upregulates Heme Oxygenase-1 in Intestinal Epithelial Cells via a Mitogen-Activated Protein Kinase- and NF-κB-Dependent Pathway, Leading to Modulation of Apoptosis. Infect Immun 84(9) 2541-54(2016) 27324483 Yeang HXA, Hamdam JM, Al-Huseini LMA, Sethu S, Djouhri L, Walsh J, Kitteringham N, Park BK, Goldring CE, Sathish JG. 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) 10556-10564(2012) 22311972 Kim H, Jung Y, Shin BS, Kim H, Song H, Bae SH, Rhee SG, Jeong W. Redox regulation of lipopolysaccharide-mediated sulfiredoxin induction, which depends on both AP-1 and Nrf2. J Biol Chem 285(45) 34419-28(2010) 20826812 Takemoto Y, Inaba S, Zhang L, Tsujikawa K, Uezumi A, Fukada SI. Implication of basal lamina dependency in survival of Nrf2-null muscle stem cells via an antioxidative-independent mechanism. J Cell Physiol 234(2) 1689-1698(2019) 30070693 Paiva CN, Feijó DF, Dutra FF, Carneiro VC, Freitas GB, Alves LS, Mesquita J, Fortes GB, Figueiredo RT, Souza HS, Fantappié MR, Lannes-Vieira J, Bozza MT. Oxidative stress fuels Trypanosoma cruzi infection in mice. J Clin Invest 122(7) 2531-42(2012) 22728935 Lou Y, Guo Z, Zhu Y, Zhang G, Wang Y, Qi X, Lu L, Liu Z, Wu J. 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(2019) 30243825 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. 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 Ethnopharmacol 168 326-36(2015) 25882312 Gatbonton-Schwager TN, Letterio JJ, Tochtrop GP. Bryonolic acid transcriptional control of anti-inflammatory and antioxidant genes in macrophages in vitro and in vivo. J Nat Prod 75(4) 591-8(2012) 22339499 Ashino T, Yamanaka R, Yamamoto M, Shimokawa H, Sekikawa K, Iwakura Y, Shioda S, Numazawa S, Yoshida T. 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 Jo C, Gundemir S, Pritchard S, Jin YN, Rahman I, Johnson GV. Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52. Nat Commun 5 3496(2014) 24667209 Tang M, Ji C, Pallo S, Rahman I, Johnson GVW. Nrf2 mediates the expression of BAG3 and autophagy cargo adaptor proteins and tau clearance in an age-dependent manner. Neurobiol Aging 63 128-139(2018) 29304346 Mendez-David I, Tritschler L, Ali ZE, Damiens MH, Pallardy M, David DJ, Kerdine-Römer S, Gardier AM. 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 597 121-6(2015) 25916883 Lou Y, Kong M, Li L, Hu Y, Zhai W, Qi X, Liu Z, Wu J. Inhibition of the Keap1/Nrf2 Signaling Pathway Significantly Promotes the Progression of Type 1 Diabetes Mellitus. Oxid Med Cell Longev 2021 7866720(2021) 33628382 Takayama K, Kaneko H, Kataoka K, Kimoto R, Hwang SJ, Ye F, Nagasaka Y, Tsunekawa T, Matsuura T, Nonobe N, Ito Y, Terasaki H. Nuclear Factor (Erythroid-Derived)-Related Factor 2-Associated Retinal Pigment Epithelial Cell Protection under Blue Light-Induced Oxidative Stress. Oxid Med Cell Longev 2016 8694641(2016) 27774118 Chen H, Li J, Li H, Hu Y, Tevebaugh W, Yamamoto M, Que J, Chen X. Transcript profiling identifies dynamic gene expression patterns and an important role for Nrf2/Keap1 pathway in the developing mouse esophagus. PLoS One 7(5) e36504(2012) 22567161 Benson SA, Ernst JD. TLR2-dependent inhibition of macrophage responses to IFN-gamma is mediated by distinct, gene-specific mechanisms. PLoS One 4(7) e6329(2009) 19629181 Suzuki R, Nakamura Y, Chiba S, Mizuno T, Abe K, Horii Y, Nagashima H, Tanita T, Yamauchi K. Mitigation of tight junction protein dysfunction in lung microvascular endothelial cells with pitavastatin. Pulm Pharmacol Ther 38 27-35(2016) 27179426 Santarino IB, Viegas MS, Domingues NS, Ribeiro AM, Soares MP, Vieira OV. Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis. Sci Rep 7(1) 5812(2017) 28724916 Tak J, Joo MS, Kim YS, Park HW, Lee CH, Park GC, Hwang S, Kim SG. Dual regulation of NEMO by Nrf2 and miR-125a inhibits ferroptosis and protects liver from endoplasmic reticulum stress-induced injury. Theranostics 14(5) 1841-1859(2024) 38505605 El Ali Z, Gerbeix C, Hemon P, Esser PR, Martin SF, Pallardy M, Kerdine-Römer S. Allergic skin inflammation induced by chemical sensitizers is controlled by the transcription factor Nrf2. Toxicol Sci 134(1) 39-48(2013) 23564646 |