B6.129S2-Rbfox1^tm1.1Dblk/J

Stock number: 014089
Research areas: Developmental Biology Research, Research Tools

Description

These mutant mice possess loxP sites flanking exons 11-12 of the Rbfox1 gene. This strain may be useful in generating conditional mutations for studying the role of Fox-1 in development and physiology of the brain, heart, and muscle tissues.

Detailed description

These Fox1^flox mutant mice possess loxP sites flanking exons 11-12 of the RNA binding protein, fox-1 homolog 1 (Rbfox1) gene. Mice that are homozygous for this allele are viable, fertile, and normal in size. Fox-1 is expressed in brain, heart, and skeletal muscle and regulates alternative splicing in vertebrates by binding specifically to (U)GCAUG sequences. When these mutant mice are bred to mice that express Cre recombinase, the resulting offspring will have exons 11-12 deleted in the Cre-expressing tissue, resulting in inactivation of Fox-1 gene function.

For example, when crossed to a strain expressing Cre recombinase in the central and peripheral nervous system (see Stock No. 003771), this mutant mouse strain may be useful in studies of neuronal excitation and seizures.

When bred to mice carrying Tg(Pcp2-cre)2Mpin (Stock No. 004146) and Rbfox2^tm1.1Dblk (Stock No. 014090) , Cre recombinase expression in the Purkinje cells may be useful in studies of Purkinje cell pacemaking.

Development

A targeting vector was designed to insert loxP sites flanking exons 11-12 of the RNA binding protein, fox-1 homolog 1 (Rbfox1) gene, followed by a frt-flanked neomycin resistance (neo) cassette. The construct was electroporated into 129S2/Sv-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric males were bred to C57BL/6J females. Offspring were bred with 129S4/SvJaeSor-Gt(ROSA)26Sor^tm1(FLP1)Dym/J transgenic mice (Stock No. 003946) to delete the neo cassette, resulting in a colony of Fox-1^flox mice. The donating investigator reported that the resulting offspring were then backcrossed to C57BL/6J mice for at least 6 generations (see SNP note below). Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Allele

Symbol: Rbfox1^tm1.1Dblk
Name: targeted mutation 1.1, Douglas Black
MGI accession ID: MGI:4838179
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Rbfox1
Marker name: RNA binding protein, fox-1 homolog (C. elegans) 1
Chromosome: 16
Strain of origin: 129S2/SvPas
Molecular note: A targeting vector was designed to insert loxP sites flanking exons 11-12 of the RNA binding protein, fox-1 homolog 1 (Rbfox1) gene, followed by a frt-flanked neomycin resistance (neo) cassette. Flp-mediated recombination removed the neo cassette leaving exons 11 and 12 floxed.