These Nfe2l2tm1Ywk (NRF2) knockout mice may be useful for studying oxidative stress in the pathogenesis of age-related macular degeneration, diabetes, Parkinson's disease, and other inflammatory degenerative diseases as well as studies of cancer, multiple sclerosis, liver cirrhosis, atherosclerosis, injury and wound healing, and more.
Michael L. Freeman, Vanderbilt University
In this NRF2 knockout strain, a β-galactosidase (lacZ) reporter followed by a neomycin resistance (neo) cassette replaces exon 5 and part of exon 4 encoding the nuclear factor, erythroid derived 2, like 2 gene (Nfe2l2) gene, abolishing gene function. Homozygotes are viable, fertile, and normal in size. NRF2, a member of the "cap 'n' collar" (CNC) subfamily of the basic region-leucine zipper transcription factors, is a regulator of endogenous antioxidant protection, microglial function, and chronic neuroinflammation. Inactivation of the CNC, DNA binding, and leucine zipper domains in Nrf2-/- mice results in age-related macular degeneration (AMD)-like retinal pathology, spontaneous choroidal neovascularization (CNV), increased sensitivity to toxins, impaired adipogenesis, abnormal mitochondria, and an increase in proinflammatory gene expression in microglia and astrocytes. The donating investigator reports that lacZ failed to generate any detectable b-galactosidase activity.
A targeting vector was designed to replace exon 5 and part of exon 4 encoding the nuclear factor, erythroid derived 2, like 2 (Nfe2l2) gene with a β-galactosidase (lacZ) reporter followed by a neomycin resistance (neo) cassette and a polyadenylation sequence. The construct was electroporated into 129X1/SvJ-derived JM-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric mice were bred to C57BL/6 mice to generate a colony of Nrf2-/- mice. The donating investigator reported that these mice were backcrossed to C57BL/6J (see SNP note below) for at least 10 generations . Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While 1 of the 27 markers throughout the genome was segregating for 129, suggested a C57BL/6 genetic background, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Yuet Wai Kan|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||NRF2-; Nrf2 KO|
|Gene Symbol and Name||Nfe2l2, nuclear factor, erythroid derived 2, like 2|
|Gene Synonym(s)||AI194320; HEBP1; NRF2; Nrf2; expressed sequence AI194320|
|Strain of Origin||129X1/SvJ|
|Mutations Made By|| |
Yuet Wai Kan, University of California SF
When maintaining a live colony, homozygous mice may be bred together. Our experience has been that homozygous breeders produced small litters and we recommend instead that either the male or female is a heterozygote.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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