Frataxin levels and pancreatic iron levels are reduced in these knock-in/knockout mice. However, unlike Friedreich's Ataxia patients, no detectable change in GAA repeat size is observed. This mutant mouse may be useful in studies of Friedreich's Ataxia.
IMR Colony, The Jackson Laboratory
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Fxn | frataxin |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Inserted expressed sequence, Humanized sequence) | Fxn | frataxin |
These frataxin knock-in/knockout (KIKO) mice harbor one allele of the frataxin (GAA)230 expansion mutation (Fxntm1Pand) on one chromosome, and one allele of the frataxin exon 4-deleted mutation (Fxntm1Mkn) on the homologous chromosome. KIKO mice are viable and fertile. Analysis of frataxin levels in tissues from KIKO mice demonstrate a reduction of frataxin to 25-36% of wildtype controls. KIKO animals up to 1 year of age perform equivalent to wildtype controls on rotarod test. Total iron concentrations were similar in all tested tissues of KIKO and wildtype mice except in pancreas: KIKO mice demonstrate lower iron levels in pancreatic tissues. No iron deposits and only mild collagen staining around the vessels of the heart were observed in both year old KIKO mice and wildtype controls. In contrast to Friedreich's Ataxia patients, no detectable change in GAA repeat size was found over six studied generations. Moreover, no evidence of somatic cell instability was noted as GAA repeat expansion size was the same in all analyzed tissues. However, characterization of KIKO mice performed at The Jackson Laboratory revealed that starting at 6 months of age, these animals exhibit an abnormal "weaving" gait when subjected to a forced treadmill walk. This phenotype occurs with increasing penetrance as the mice age. This mutant mouse may be useful in studies of Friedreich's Ataxia.
Importation of this model was supported by the Friedreich's Ataxia Research Alliance (FARA).
To generate these frataxin knock-in/knockout animals (KIKO), mice heterozygous for the frataxin (GAA)230 expansion mutation (Fxntm1Pand) were bred with mice heterozygous for the frataxin exon 4-deleted mutation (Fxntm1Mkn). Progeny bearing both the GAA expansion (knock-in) allele and the exon 4-deleted (knockout) allele were bred together, and given the Stock No. 014162. These KIKO mice no longer harbor the Tg(FXN)YG8Pook transgene.
For a description of the frataxin (GAA)230 expansion mutation (Fxntm1Pand), please see Stock No. 008470.
For a description of the frataxin exon 4-deleted mutation (Fxntm1Mkn), please see the compound mutant Stock No. 012253.
Expressed Gene | Fxn, frataxin, mouse, laboratory |
---|---|
Site of Expression | |
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. |
Allele Name | targeted mutation 1, Massimo Pandolfo |
---|---|
Allele Type | Targeted (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | frda230GAA |
Gene Symbol and Name | Fxn, frataxin |
Gene Synonym(s) | |
Promoter | Fxn, frataxin, mouse, laboratory |
Strain of Origin | 129/Sv |
Chromosome | 19 |
Molecular Note | A targeting vector was designed to insert a GAA230 repeat expansion and a floxed neomycin resistance cassette into intron 1 of the locus. Western blot demonstrated that mutants expressed frataxin protein at 75% of wild-type levels in all tissues examined. |
Mutations Made By | Massimo Pandolfo, Universite Libre de Bruxelles |
When maintaining the live KIKO colony, animals harboring one allele of the frataxin (GAA)230 expansion mutation (Fxntm1Pand) on one chromosome, and one allele of the frataxin exon 4-deleted mutation (Fxntm1Mkn) on the homologous chromosome may be bred together.
When using the KIKO mouse strain in a publication, please cite the originating article(s) and include JAX stock #014162 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Fxn<tm1Mkn>Heterozygous or wildtype for Fxn<tm1Pand> |
Frozen Mouse Embryo | B6.Cg-Fxn<tm1Mkn> Fxn<tm1Pand>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.Cg-Fxn<tm1Mkn> Fxn<tm1Pand>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.Cg-Fxn<tm1Mkn> Fxn<tm1Pand>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.Cg-Fxn<tm1Mkn> Fxn<tm1Pand>/J Frozen Embryo | $3373.50 |
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