B6.Cg-Tg(FXN*)1Sars Fxn^tm1Mkn rd21/BocJ

Stock number: 036965
Research areas: Sensorineural Research

Description

The retinal degeneration 21 (rd21) heritable phenotype causes attenuated retinal vessels beginning around 5 months of age with progression to retinal degeneration by 7 months of age. This phenotype maps to the interval containing Fxn and it has not yet been determined whether this phenotype is due to Fxn^tm1Mkn.

Detailed description

Late-onset photoreceptor degeneration and retinal detachment are the eventual characteristics of the rd21 heritable phenotype. Electroretinograms from rd21 homozygotes showed lower a-wave and near-normal b-wave in rod response at 4 months of age, normal cone responses at 5 months of age, but neither rod nor cone waveforms were detectable at 8 months of age. At 5 months of age attenuated retinal vessels were observed, at 6 months of age 20-30% photoreceptor loss and areas of depigmentation were found, and at 7 months of age the phenotype reached complete photoreceptor degeneration and retinal detachment. This phenotype mapped near D19Mit61 to a Chromosome 19 interval containing Fxn and it has not yet been determined whether this phenotype is due to Fxn^tm1Mkn or a mutation in some other nearby gene.

Development

The retinal degeneration 21 heritable phenotype (rd21) was identified in the strain B6.Cg-Tg(FXN*)1Sars Fxn/J. For mapping purposes an outcross to C57BL/6J was done and the unaffected F1 hybrid population was intercrossed to generate homozygotes. The strain was then maintained by sibling intercrossing affected rd21 homozygotes. The mapping data placed the rd21 phenotype in the area of the Fxn gene and this strain was found to be homozygous for both Tg(FXN*)1Sars and Fxn^tm1Mkn, allowing for the possibility that the rd21 phenotype is due to the Fxn^tm1Mkn allele. Sperm was cryopreserved from homozygotes at generation N1F15.

Allele

Symbol: Fxn^tm1Mkn
Name: targeted mutation 1, Michel Koenig
MGI accession ID: MGI:2177162
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Frda^-; Frda^del4
Marker symbol: Fxn
Marker name: frataxin
Marker synonyms: CyaY; FA; FARR; FRDA; RGD1565754; X25
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.

Allele

Symbol: rd21
Name: retinal degeneration 21
MGI accession ID: MGI:5906381
Generation method: Spontaneous
Attributes: Not Specified
Marker symbol: rd21
Marker name: retinal degeneration 21
Chromosome: 19
Strain of origin: B6.Cg-Tg(FXN*)1Sars Fxn^tm1Mkn/J
Molecular note: This spontaneous mutation has been mapped to Chromosome 19 with close linkage to D19Mit61.