STOCK Tg(FXN*)1Sars Fxn^tm1Mkn/J

Stock number: 018299
Product name: FVB;B6.Tg(FXN);Fxn-
Research areas: Neurobiology Research

Description

These FVB;B6.Tg(FXN);Fxn- mice harbor the the FXN*500GAA transgene (Tg(FXN)1Sars) and frataxin knockout allele (Fxn^tm1Mkn), and may be useful in studying Friedreich's Ataxia. Because FVB;B6.Tg(FXN);Fxn- mice were bred onto the FVB/NJ genetic background for one generation, they may also allow larger litters compared to the C57BL/6-congenic Tg(FXN);Fxn- strain (Stock No. 008586).

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Detailed description

FVB;B6.Tg(FXN);Fxn- mice (Stock No. 018299) harbor the the FXN*500GAA transgene (Tg(FXN)1Sars) and frataxin knockout allele (Fxn^tm1Mkn), and may be useful in studying Friedreich's Ataxia. Because FVB;B6.Tg(FXN);Fxn- mice were bred onto the FVB/NJ genetic background for one generation, they may also allow larger litters compared to the C57BL/6-congenic Tg(FXN);Fxn- strain (Stock No. 008586). Mice hemizygous for the transgene and homozygous for the knockout allele (FVB;B6.Tg(FXN);Fxn-/-) are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

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. It should be noted that the phenotype of FVB;B6.Tg(FXN);Fxn- mice (Stock No. 018299) could vary from that originally described for the C57BL/6-congenic Tg(FXN);Fxn- strain (Stock No. 008586). We will modify the strain description for FVB;B6.Tg(FXN);Fxn- mice if necessary as published results become available.
To date (November 2015) the phenotype of the C57BL/6-congenic Tg(FXN);Fxn- strain (Stock No. 008586) lists that mice hemizygous for the transgene and homozygous for the knockout allele (Tg(FXN);Fxn-/-) are viable, normal in size and do not display any gross physical or behavioral abnormalities. The donating investigator reports that no other behavioral or histological phenotype has been observed. FISH and karyotyping shows one copy of the transgene inserted on chromosome 5.

Development

FVB;B6.Tg(FXN);Fxn- mice (Stock No. 018299) harbor the the FXN*500GAA transgene (Tg(FXN)1Sars) and frataxin knockout allele (Fxn^tm1Mkn) from Stock No. 008586.

The FVB;B6.Tg(FXN);Fxn- strain (Stock No. 018299) was created by first breeding FVB/NJ females (Stock No. 001800) with C57BL/6J-congenic males hemizygous for the FXN*500GAA transgene and homozygous for the frataxin knockout allele (Tg(FXN);Fxn-/- ; from Stock No. 008586). The resulting F1 offspring ([FVBxB6]F1.HEMI;HET and [FVBxB6]F1.NCar;HET) were then bred together to produce F2 animals. The resulting F2 animals were bred together to generate the next intercross generation (F3). The strain was then maintained by continued intercrossing of FVB;B6.HEMI;HET, FVB;B6.NCar;HET, FVB;B6.HEMI;HOM, and/or FVB;B6.NCar;HOM.

The FXN*500GAA transgene, created by Dr. Joseph Sarsero, was designed with a bacterial artificial chromosome (BAC) containing the entire human frataxin (FXN) gene with an interrupted 500 GAA trinucleotide repeat inserted into intron 1. FISH and karyotyping of mice from founder line 1 shows one copy of the transgene inserted on chromosome 5.

The frataxin knockout allele (Frda^- or Frda^del4) was designed by Drs. Michel Koenig and Helene Puccio by replacing exon 4 of the frataxin gene on chromosome 19 with a loxP-flanked PGK-neomycin resistance cassette.

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: Tg(FXN*)1Sars
Name: transgene insertion 1, Joseph Sarsero
MGI accession ID: MGI:5432794
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(FXN*)1Sars
Marker name: transgene insertion 1, Joseph Sarsero
Chromosome: 5
Strain of origin: C57BL/6J
Expressed genes: FXN,frataxin,human
Molecular note: The transgene contained a bacterial artificial chromosome (BAC) with the entire human frataxin (FXN) gene with a 500 GAA trinucleotide repeat inserted into intron 1. Line 1 contained a single copy of the transgene inserted into chromosome 5.