B6.Cg-Foxp2^tm1.1Sfis/CfreJ

Stock number: 026259
Product name: Foxp2^floxΔneo
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

The Foxp2^floxΔneo allele has loxP sites flanking the DNA-binding motif (exons 12-14) of the forkhead box P2 gene. The mice allow Cre recombinase-inducible Foxp2 knockout, and may be useful for studying speech and language development during embryogenesis/neurogenesis, speech impairment, dyslexia, cognitive function/flexibility, sensorimotor integration and motor-skill learning.

Detailed description

The Foxp2^floxΔneo floxed allele has loxP sites flanking the DNA-binding motif (exons 12-14) of forkhead box P2 (Foxp2). These Foxp2^floxΔneo mice allow Cre recombinase-inducible Foxp2 knockout (as shown by loss of the floxed exons at the RNA level and an absence of Foxp2 protein).

Foxp2 is a transcription factor, and disruptions of the human protein result in a severe speech and language disorder. Foxp2 is expressed in neuronal subpopulations of several brain regions during embryogenesis and in adulthood, and is also found in other areas such as the lung, gut and spinal cord. It is involved in the processes of neurite outgrowth and synaptic plasticity and is important for sensorimotor integration and motor-skill learning

Mice homozygous for the Foxp2^floxΔneo allele are viable and fertile with no reported gross physical or behavioral abnormalities.

Development

The Foxp2^floxΔneo allele was created by Drs. Simon E. Fisher and Catherine A. French (while at The Wellcome Trust Centre for Human Genetics, Oxford University). A targeting vector was designed to insert a loxP site followed by a self-excising frt-flanked neomycin resistance (neo) cassette upstream of exon 12, and a second loxP site downstream of exon 14 of the forkhead box P2 gene (Foxp2) on chromosome 6. The construct was electroporated into B6.Cg-Thy1^a-derived Bruce 4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric males were bred to C57BL/6 albino females (C57BL/6J-Tyr^c-2J). The offspring still harbored the self-excising frt-flanked neo cassette (Foxp2^floxneo), and were therefore bred to ACTB-FLPe transgenic mice (C57BL/6J genetic background; Stock No. 005703) to delete the neo cassette. The resulting Foxp2^floxΔneo mice were bred with C57BL/6J wildtype animals to remove the Flp-expressing transgene. Foxp2^floxΔneo mice were bred with C57BL/6J mice for at least ten generations. The donating investigator reports that during backcrossing, the Y chromosome was fixed to the C57BL/6J genetic background. In 2015, Dr. French (Champalimaud Centre for the Unknown, Portugal) sent black males to The Jackson Laboratory. Upon arrival, males were used to cryopreserve sperm. To establish the living Foxp2^floxΔneo mouse colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6J inbred females (Stock No. 000664).

Allele

Symbol: Foxp2^tm1.1Sfis
Name: targeted mutation 1.1, Simon E Fisher
MGI accession ID: MGI:3723629
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Foxp2
Marker name: forkhead box P2
Chromosome: 6
Strain of origin: B6.Cg-Thy1^a
Molecular note: Flp-mediated recombination was used to remove the FLPe-neo cassette between exons 11 and 12 leaving a floxed exon 12 through 14 region.