Fxnnull mice harbor a frataxin global knockout allele that is embryonic lethal when homozygous. Along with the Cre-conditional frataxin floxed exon 2 allele (Fxnflox; Stock No. 028520), they may be useful in studying Friedreich's Ataxia. In addition, these mice were used to generate the progressive cardiomyopathy mouse line Fxnflox/null::MCK-Cre (Stock No. 029720).
Cathleen Lutz, The Jackson Laboratory
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 global knockout allele Fxnnull (Fxnem2.1Lutzy) has exon 2 deleted. Mice heterozygous for this allele are viable and fertile with no reported gross phenotypic or behavioral abnormalities. Mice homozygous for the frataxin global knockout allele are embryonic lethal.
The global knockout allele of mouse frataxin Fxnnull (Fxnem2.1Lutzy) was made by Dr. Cat Lutz at The Jackson Laboratory.
First, the frataxin floxed exon 2 allele Fxnflox (Fxnem2Lutzy) was created using CRISPR/cas9 endonuclease-mediated genome editing. Plasmids encoding a signal 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.
To generate the frataxin global knockout allele Fxnnull (Fxnem2.1Lutzy), male mice carrying the floxed exon 2 allele (from Stock No. 028520) were bred to female B6N.Cg-Tg(Sox2-cre)1Amc/J (Stock No. 014094). The resulting mice (exon 2 deleted from germline) were further bred to C57BL/6J to breed out the Cre recombinase transgene. Heterozygous intercrosses were performed to confirm the embryonic lethality of the null allele. Mice heterozygous for this frataxin global knockout allele are available as Stock No. 028040.
|Allele Name||endonuclease-mediated mutation 2.1, Cathy Lutz|
|Allele Type||Endonuclease-mediated (Null/Knockout)|
|Gene Symbol and Name||Fxn, frataxin|
|Site of Expression||Cardiac and skeletal muscle.|
|Strain of Origin||C57BL/6J|
|Molecular Note||CRISPR/Cas9 genome editing was used to introduce loxP sites flanking exon 2. Cre-mediated recombination removed exon 2.|
Mice heterozygous for the frataxin global knockout allele are viable and fertile with no reported gross phenotypic or behavioral abnormalities. Mice homozygous for the frataxin global knockout allele are embryonic lethal.
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664).
When using the Fxnnull (exon 2 deleted) mouse strain in a publication, please cite the originating article(s) and include JAX stock #028040 in your Materials and Methods section.