These Frdadel4 Fxn knockout mice exhibit an embryonic lethal phenotype and are useful in studies of in studies of Friedreich's ataxia.
Michel Koenig, IGBMC/CNRS/INSERM/Université Louis Pasteur Hopitaux/Université de Strasbourg
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Fxn | frataxin |
Frataxin mitochondrial protein, which is encoded by the Fxn gene, regulates mitochondrial iron transport and respiration. Expansion of the intronic GAA nucleotide repeat causes Friedreich's ataxia. These Frdadel4 mice carry a knock out mutation for the Fxn gene in which exon 4 has been replaced by a floxed PGK-NEO cassette. Mice that are heterozygous for the targeted mutation are viable and fertile.
No gene product (protein) is detected by Western blot analysis of rescued double mutant mice that are homozygous for this null allele and are carrying the Tg(FXN)Y47Pook transgene (see Stock#024097).
Homozygous null mice have an early post-implantation lethal phenotype, and are resorbed by E9.5. By E7, homozygous embryos and extra-embryonic tissues are smaller in size than wildtype controls. At E6.75 and E7.5, homozygous embryos exhibit pycnotic nuclei and condensed chromatin; extra-embryonic regions exhibit clusters of apoptotic TUNEL-positive cells. Necrotic cells are also observed.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
Importation of this model was supported by the Friedreich's Ataxia Research Alliance (FARA).
Drs. Michel Koenig and Helene Puccio generated the Fxn targeted mutation allele by disrupting exon 4 and flanking sequences with a loxP site flanked PGK-neo cassette. The construct was electroporated into 129/Sv derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice. The mice were crossed to a transgenic line on the C57BL/6 background, and the double mutant mice were backcrossed to C57BL/6J using a speed congenic protocol. The mice were then bred to remove the transgene.
Expressed Gene | Fxn, frataxin, mouse, laboratory |
---|---|
Site of Expression |
Allele Name | targeted mutation 1, Michel Koenig |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Frda-; Frdadel4 |
Gene Symbol and Name | Fxn, frataxin |
Gene Synonym(s) | |
Expressed Gene | Fxn, frataxin, mouse, laboratory |
Strain of Origin | 129/Sv |
Chromosome | 19 |
Molecular Note | A loxP-flanked PGK-neomycin resistance cassette replaced a genomic DNA fragment containing exon 4, which is highly conserved and often mutated in humans. An additional line was also produced in which the loxP flanked neomycin cassette was removed by Cre mediated recombination, but no distinction was made between these alleles in the original reference. From J:90098: The presence of a human FRDA transgene in hemizygous form in a Frdatm1Mkn homozygous null background rescues the embryonic lethal phenotype and complements for the loss of endogenous mouse frataxin. |
When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664). Homozygotes are not viable.
When using the B6.129(Cg)-Fxntm1Mkn/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #016842 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Fxn<tm1Mkn> |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.