Strain Data Sheet

RBRC00984

Strain Information

Image
BRC No.RBRC00984
TypeTargeted MutationCartagena
SpeciesMus musculus
Strain nameICR;129P2-Nfe2l2<tm1Mym>/MymRbrc
Former Common nameNrf2 knock out mouse (ICR background)
H-2 Haplotype
ES Cell lineE14 [129P2/OlaHsd]
Background strainJcl:ICR
Appearance
Strain developmentDeveloped 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 descriptionNrf2 (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 maintenanceHomozygote x Heterozygote [or Crossing to Jcl:ICR]
References
An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements.
Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M, Nabeshima Y
Biochem. Biophys. Res. Commun., 236, 313-322 (1997). 9240432

Health Report

Examination Date / Room / Rack

Gene

Gene SymbolGene NameChr.Allele SymbolAllele NameCommon NamesPromoterDiseases Related to This Gene
Nfe2l2
MGI:108420		nuclear factor, erythroid derived 2, like 22Nfe2l2<tm1Mym>
MGI:2385925		targeted mutation 1, Masayuki Yamamoto
  • immunodeficiency, developmental delay, and hypohomocysteinemia(MedGEN)
    • lacZ beta-galactosidase (E. coli)2
    neo neomycin resistance gene (E. coli)2 herpes simplex virus thymidine kinase promoter (HSV tk promoter)
    nls SV40 large T antigen nuclear localization signal (NLS)2nls

    Phenotype

    Annotation by Mammalian phenotyhpe ontology
  • abnormal behavior(MP:0004924)

  • abnormal enamel morphology(MP:0002576)

  • abnormal glomerular capillary morphology(MP:0011320)

  • abnormal glomerular mesangium morphology(MP:0011339)

  • abnormal incisor color(MP:0010096)
    • more 51 phenotypes
  • abnormal iron homeostasis(MP:0005637)

  • abnormal iron level(MP:0001770)

  • abnormal leukocyte adhesion(MP:0003628)

  • abnormal macrophage physiology(MP:0002451)

  • abnormal physiological response to xenobiotic(MP:0008872)

  • abnormal renal glomerulus morphology(MP:0005325)

  • abnormal respiratory system physiology(MP:0002133)

  • abnormal tooth morphology(MP:0002100)

  • ameloblast degeneration(MP:0000129)

  • cachexia(MP:0005150)

  • circling(MP:0001394)

  • decreased CD4-positive, alpha-beta T cell number(MP:0008075)

  • decreased T cell number(MP:0005018)

  • decreased body weight(MP:0001262)

  • decreased creatinine clearance(MP:0005558)

  • decreased urine creatinine level(MP:0011471)

  • enlarged lymph nodes(MP:0000702)

  • glomerular crescent(MP:0011506)

  • glomerulonephritis(MP:0002743)

  • glomerulosclerosis(MP:0005264)

  • hematopoietic system phenotype(MP:0005397)

  • hepatic steatosis(MP:0002628)

  • homeostasis/metabolism phenotype(MP:0005376)

  • hypoglycemia(MP:0000189)

  • increased IgG level(MP:0002493)

  • increased IgM level(MP:0002494)

  • increased acute inflammation(MP:0005088)

  • increased anti-double stranded DNA antibody level(MP:0004762)

  • increased anti-nuclear antigen antibody level(MP:0004794)

  • increased cerebral infarct size(MP:0006060)

  • increased circulating alanine transaminase level(MP:0002941)

  • increased circulating interleukin-6 level(MP:0008596)

  • increased circulating tumor necrosis factor level(MP:0008553)

  • increased hepatocyte apoptosis(MP:0003887)

  • increased incidence of tumors by chemical induction(MP:0004499)

  • increased kidney cell proliferation(MP:0011440)

  • increased liver iron level(MP:0008807)

  • increased lung weight(MP:0005630)

  • increased mesangial cell number(MP:0011427)

  • increased spleen weight(MP:0004952)

  • increased stomach tumor incidence(MP:0010301)

  • increased susceptibility to experimental autoimmune uveoretinitis(MP:0004821)

  • increased susceptibility to induced colitis(MP:0008537)

  • increased susceptibility to ischemic brain injury(MP:0003076)

  • increased susceptibility to xenobiotic induced morbidity/mortality(MP:0009766)

  • increased urine protein level(MP:0002962)

  • liver inflammation(MP:0001860)

  • lung inflammation(MP:0001861)

  • oxidative stress(MP:0003674)

  • pulmonary fibrosis(MP:0006050)

  • weight loss(MP:0001263)
    • Detailed phenotype data

    Ordering Information

    Donor DNASimian 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
    Specific Term and ConditionsThe 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). In publishing the research results to be obtained by use of the BIOLOGICAL RESOURCE, an acknowledgment to the DEPOSITOR is requested. The depositor should be a co-author in the articles when the users publish their data using these mice for 2 year after provided.
    Any patent rights and other intellectual properties are retained by the depositor. Users should contact the depositor in the case of application for any patents with the results from these mice.
    DepositorMasayuki Yamamoto (University of Tsukuba)
    Strain Statusan icon for Frozen embryosFrozen embryos
    an icon for Frozen spermFrozen sperm
    Strain AvailabilityRecovered litters from cryopreserved embryos (2 to 4 months)
    Cryopreserved sperm (within 1 month)
    Cryopreserved embryos (within 1 month)
    Additional Info.Necessary documents for ordering:
    1. Approval form (Japanese / English)
    2. Order form (Japanese / English)
    3. Category I MTA: MTA for distribution with RIKEN BRC (Japanese / English)
    4. Acceptance of responsibility for living modified organism (Japanese / English)
    Lab HP (Japanese)
    Genotyping protocol -PCR-
    Mouse of the Month Oct 2005
    Mouse of the Month Apr 2012

    BRC mice in Publications

    Ramkissoon A, Wells PG.
    Methamphetamine oxidative stress, neurotoxicity, and functional deficits are modulated by nuclear factor-E2-related factor 2.
    Free Radic Biol Med 89 358-68(2015) 26427884
    Ramkissoon A, Wells PG.
    Developmental role of nuclear factor E2-related factor 2 in mitigating methamphetamine fetal toxicity and postnatal neurodevelopmental deficits.
    Free Radic Biol Med 65 620-631(2013) 23932974
    Clarke JD, Hsu A, Williams DE, Dashwood RH, Stevens JF, Yamamoto M, Ho E.
    Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice.
    Pharm Res 28(12) 3171-9(2011) 21681606
    Gebel S, Diehl S, Pype J, Friedrichs B, Weiler H, Schüller J, Xu H, Taguchi K, Yamamoto M, Müller T.
    The transcriptome of Nrf2-/- mice provides evidence for impaired cell cycle progression in the development of cigarette smoke-induced emphysematous changes.
    Toxicol Sci 115(1) 238-52(2010) 20133372
    Ho E, Clarke JD, Dashwood RH.
    Dietary sulforaphane, a histone deacetylase inhibitor for cancer prevention.
    J Nutr 139(12) 2393-6(2009) 19812222