B6.Cg-Fxn^tm1.1Pand Fxn^tm1Mkn/J

Stock number: 012329
Product name: KIKO FA
Research areas: Neurobiology Research

Description

These frataxin knock-in/knock-out mice may be useful in studies of Friedreich's Ataxia.

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Detailed description

These frataxin knock-in/knock-out animals (KIKOΔneo) mice harbor one allele of the frataxin (GAA)₂₃₀Δneo expansion mutation (Fxn^tm1.1Pand) on one chromosome, and one allele of the frataxin exon 4-deleted mutation (Fxn^tm1Mkn) on the homologous chromosome. This is similar to frataxin KIKO mice (Stock No. 014162), with the exception that these KIKOΔneo mice have the (GAA)₂₃₀ expansion allele with the neo selection cassette removed. 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.

Importation of this model was supported by the Friedreich's Ataxia Research Alliance (FARA).

Development

To generate these frataxin knock-in/knock-out animals (KIKOΔneo), C57BL/6J-congenic mice heterozygous for the frataxin (GAA)₂₃₀ expansion mutation (Fxn^tm1Pand; Stock No. 008470) were first bred with C57BL/6-congenic mice harboring the embryonic cre-expressing mutation Meox2-Cre (Meox2^tm1(cre)Sor; Stock No. 003755). Progeny bearing the GAA expansion with the neo selection cassette deleted ((GAA)₂₃₀Δneo ; Fxn^tm1.1Pand) were bred together, and the Meox2-Cre mutation was selectively removed. These (GAA)₂₃₀Δneo "knock-in" mice were given the Stock No. 011113. Next, the (GAA)₂₃₀Δneo mice were bred with C57BL/6J-congenic mice heterozygous for the frataxin exon 4-deleted mutation (Fxn^tm1Mkn; from Stock No. 012253). Progeny bearing both the (GAA)₂₃₀Δneo (knock-in) allele and the exon 4-deleted (knock-out) allele were bred together, and given the Stock No. 012329. These KIKOΔneo mice no longer harbor the Tg(FXN)YG8Pook transgene. To maintain the live colony, females homozygous for the (GAA)₂₃₀Δneo allele (Fxn^tm1.1Pand) are bred with males heterozygous for the exon 4-deleted mutation (Fxn^tm1Mkn) every generation.

Allele

Symbol: Fxn^tm1Mkn
Name: targeted mutation 1, Michel Koenig
MGI accession ID: MGI:2177162
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Fxn
Marker name: frataxin
Chromosome: 19
Strain of origin: 129/Sv
Expressed genes: Fxn,frataxin,mouse, laboratory
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 Frda^tm1Mkn homozygous null background rescues the embryonic lethal phenotype and complements for the loss of endogenous mouse frataxin.

Allele

Symbol: Fxn^tm1.1Pand
Name: targeted mutation 1.1, Massimo Pandolfo
MGI accession ID: MGI:4881494
Generation method: Targeted
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Fxn
Marker name: frataxin
Chromosome: 19
Strain of origin: 129/Sv
Molecular note: Mice carrying the Fxn^tm1Pand allele were crossed with mice carrying the Meox2^tm1(cre)Sor allele to remove the neomycin cassette, leaving an insertion of a GAA230 repeat expansion.