129S.B6(SJL)-Fgf13^{tm1c(EUCOMM)Wtsi}/GolJ

Stock number: 036280
Product name: Fhf2^fl
Research areas: Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Internal/Organ Research, Neurobiology Research, Research Tools

Description

Fhf2^fl/fl floxed mice have loxP sites flanking exon 3 of the X-linked fibroblast growth factor 13 (Fgf13) gene. These mice are useful for studying the effects of sodium channel inactivation on cardiac conduction failure.

Detailed description

Fhf2^fl/fl floxed mice have loxP sites flanking exon 3 of the X-linked fibroblast growth factor 13 (Fgf13) gene. Also called Fhf2, Fgf13 is an X-linked gene and is a key regulator of sodium channel (NaV) inactivation. Mutations in FHFs have been implicated in human diseases including Brugada syndrome, idiopathic ventricular arrhythmias, and epileptic encephalopathy. Brugada syndrome is an arrhythmic condition associated with sodium channel loss-of-function. Homozygous female and hemizygous male floxed mice are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 3 deleted in the Cre-expressing tissues. The donating investigator reports that resulting Fhf2^KO mice are not viable on a C57BL/6 genetic background.

When bred to mice expressing Cre recombinase, resulting Fhf2^KO mice have no FHF2 expressed in the heart and brain tissue. The KO mice exhibit defects in sodium channel inactivation that give rise to severe conduction defects in the heart. Increasing core body temperature by as little as 3 degrees C causes temperature-sensitive electrocardiographic changes that are fully reversible upon return to normothermia.

Development

The L1L2_Bact_P cassette was inserted at a position on Chromosome X upstream of exon 3 of the fibroblast growth factor 13 (Fgf13) gene. The cassette is composed of a frt site, a lacZ sequence, and a loxP site followed by a neomycin resistance cassette, a second frt site, and a second loxP site. A third loxP site was inserted downstream of exon 3. The mutation was generated in C57BL/6N-A^tm1Brd derived JM8A1.N3 embryonic stem (ES) cells, and correctly targeted ES cells of clone EPD0339_4_F09 were injected into blastocysts. The resulting chimeric mice were bred to 129S2 mice and then subsequently to ACTB:FLPe transgenic mice (Stock No. 005703) to remove the frt-flanked lacZ sequence and neomycin cassette. Resulting Fhf2^fl/fl mice were bred to 129S2 mice for at least 4 generations. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize 129S1/SvImJ oocytes (Stock No. 002448).

Allele

Symbol: Fgf13^{tm1c(EUCOMM)Wtsi}
Name: targeted mutation 1c, Wellcome Trust Sanger Institute
MGI accession ID: MGI:6704911
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Fhf2^fl; Fhf2^flox
Marker symbol: Fgf13
Marker name: fibroblast growth factor 13
Marker synonyms: DEE90; FGF-13; Fgf1c; FGF2; Fhf2; FHF-2; LINC00889; XLID110
Chromosome: X
Strain of origin: C57BL/6N-A^tm1Brd
Molecular note: FLP-mediated recombination removed the lacZ and neomycin cassette from Fgf13^{tm1a(EUCOMM)Wtsi}.