Generation of an allele to inactivate Wnt4 gene function conditionally in the mouse.
The Wnt family member Wnt4 is critical for the development of several organs, including the kidney, gonad, and adrenal, mammary, and pituitary glands. To study its potential postnatal functions, we generated a floxed Wnt4 allele. A single loxP site was targeted to the second intron, while a loxP-Neo-loxP cassette was placed 3' from Exon 5. The floxed Neo cassette was subsequently removed by crossing with MeuCre40 transgenic mice. The Wnt4 gene was specifically inactivated with CAGCre and another Wnt4 allele, Wnt4(EGFPCre), in which the Cre is driven by the endogenous Wnt4 promoter. Deletion of Wnt4 gene function with CAGCre impaired kidney development, as is the case with the conventional knockout. Similarly, the Wnt4(EGFPCre)-mediated inactivation of Wnt4 function considerably reduced the amount of Wnt4 transcripts, led to a severe defect in kidney development, and caused the female embryos to undergo partial sex reversal to males. All in all, the floxed Wnt4 allele serves as a useful tool for studying the roles of Wnt4 signaling during the life cycle.
Shan
Jingdong
J
Oulu Center for Cell-Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology, Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland.
Jokela
Tiina
T
Peltoketo
Hellevi
H
Vainio
Seppo
S
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005838:Genotype; D007668:Kidney / Q000196:embryology; D008297:Male; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051153:Wnt Proteins / Q000235:genetics*; D060528:Wnt4 Protein
D017931:DNA Primers; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse