Abstract
Disruptions of the human FOXP2 gene cause problems with articulation of complex speech sounds, accompanied by impairment in many aspects of language ability. The FOXP2/Foxp2 transcription factor is highly similar in humans and mice, and shows a complex conserved expression pattern, with high levels in neuronal subpopulations of the cortex, striatum, thalamus, and cerebellum. In the present study we generated mice in which loxP sites flank exons 12–14 of Foxp2; these exons encode the DNA-binding motif, a key functional domain. We demonstrate that early global Cre-mediated recombination yields a null allele, as shown by loss of the loxP-flanked exons at the RNA level and an absence of Foxp2 protein. Homozygous null mice display severe motor impairment, cerebellar abnormalities and early postnatal lethality, consistent with other Foxp2 mutants. When crossed to transgenic lines expressing Cre protein in a spatially and/or temporally controlled manner, these conditional mice will provide new insights into the contributions of Foxp2 to distinct neural circuits, and allow dissection of roles during development and in the mature brain. genesis 45:440–446, 2007. Published 2007 Wiley-Liss, Inc.
Highlights
Heterozygous Foxp2D12–14/þ pups display no overt abnormalities—they gain weight at the same rate as their wildtype littermates, do not show significant righting deficits, and have normal cerebellar size and foliation (Fig. 3c–f). Phenotypes of these homozygous and heterozygous animals are highly consistent with those observed in mutant mice carrying an early stop codon in exon 7 of Foxp2 (Groszer et al, in preparation)
Exon numbering for murine Foxp2 is concordant with that found for orthologous exons in human FOXP2 (MacDermot et al, 2005), C57BL/6 DNA containing exons 11–16 of Foxp2 was cloned into the vector pEASY-FLIRT (Casola, 2004)
Speech and language impairment and oromotor dyspraxia due to deletion of 7q31 that involves FOXP2
Summary
Heterozygous Foxp2D12–14/þ pups display no overt abnormalities—they gain weight at the same rate as their wildtype littermates, do not show significant righting deficits, and have normal cerebellar size and foliation (Fig. 3c–f) Phenotypes of these homozygous and heterozygous animals are highly consistent with those observed in mutant mice carrying an early stop codon in exon 7 of Foxp (Groszer et al, in preparation). Crossing our floxed line with transgenic mice which express Cre-recombinase in a spatially and/or temporally controlled manner should circumvent problems associated with early postnatal lethality and allow investigations of adult animals Such studies will facilitate investigations of Foxp function in the various tissues where it is expressed, including brain, lung, intestine, and cardiovascular system. Our conditional allele represents a powerful tool for dissecting the differential contributions of Foxp to development and function of distinct neural networks in the mammalian central nervous system
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
