C57BL/6J-Fxn^em2Lutzy/J

Stock number: 028520
Product name: Fxn^flox (floxed exon 2)
Research areas: Cardiovascular Research, Neurobiology Research, Research Tools

Description

Fxn^flox (floxed exon 2) mice have a CRISPR/Cas9-generated, Cre-conditional frataxin allele - and may be useful in studying Friedreich's Ataxia. In addition, these mice are a parental control used to generate the progressive cardiomyopathy mouse line Fxn^flox/null::MCK-Cre (Stock No. 029720) and the Friedreich's Ataxia mouse model, Fxn^flox/null::PV-Cre (Stock No. 029721).

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Detailed description

The mitochondrial frataxin protein (encoded by Fxn) is involved in mitochondrial iron transport and respiration regulation. FXN mutations are associated with Friedreich's Ataxia.
The frataxin floxed exon 2 allele (Fxn^flox) has loxP sites flanking exon 2. Mice homozygous for this floxed allele are viable and fertile with no reported gross phenotypic or behavioral abnormalities.
Upon exposure to Cre recombinase, the floxed sequences are deleted - resulting in a null allele. For example, breeding to germline Cre-expressing mice (e.g., Sox2-Cre; Stock No. 014094) generates mice with the frataxin global knockout allele (Fxn^null; Stock No. 028040). Mice homozygous for the global knockout allele (Fxn^null/null) exhibit embryonic lethality.

Development

The frataxin floxed exon 2 allele (Fxn^flox ; Fxn^em2Lutzy) was made by Dr. Cat Lutz at The Jackson Laboratory using CRISPR/cas9 endonuclease-mediated genome editing. Plasmids encoding a single guide RNA designed to introduce loxP sites flanking exon 2 in the Fxn gene and the CRISPR/cas9 nuclease were introduced into the cytoplasm C57BL/6J-derived fertilized eggs with well recognized pronuclei. Correctly targeted embryos were transferred to pseudopregnant females. Correctly targeted pups were identified by sequencing and PCR. Mice from founder 466 were further bred to C57BL/6J inbred mice (Stock No. 000664) to develop the frataxin floxed exon 2 colony as Stock No. 028520.

Allele

Symbol: Fxn^em2Lutzy
Name: endonuclease-mediated mutation 2, Cathy Lutz
MGI accession ID: MGI:5825257
Generation method: Endonuclease-mediated
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Fxn
Marker name: frataxin
Chromosome: 19
Strain of origin: C57BL/6J
Molecular note: CRISPR/Cas9 genome editing is used to introduce loxP sites flanking exon 2.