title: Generation of mice with a conditional Foxp2 null allele.
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.
authors.affiliation: The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: French
authors.forename: Matthias
authors.initials: M
authors.lastname: Groszer
authors.forename: Christopher
authors.initials: C
authors.lastname: Preece
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Coupe
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
authors.forename: Simon E
authors.initials: SE
authors.lastname: Fisher
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000002:abnormalities; D005260:Female; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009422:Nervous System Diseases / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D051858:Forkhead Transcription Factors; C432918:Foxp2 protein, mouse; D012097:Repressor Proteins