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Generation of an allele to inactivate Wnt4 gene function conditionally in the mouse
Jingdong Shan1, Tiina Jokela, Hellevi Peltoketo
1Oulu Center for Cell-Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology, Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland.
Abstract:
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.
Insights
The Wnt4 gene is essential for organ development. Researchers created a new Wnt4 tool to study its postnatal functions, revealing its critical role in kidney development and sex determination.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Wnt4 is a crucial Wnt family member involved in the development of multiple organs.
- Understanding the postnatal functions of Wnt4 is important for developmental studies.
Purpose of the Study:
- To generate a novel floxed Wnt4 allele for studying its postnatal functions.
- To investigate the specific roles of Wnt4 in kidney development and sex determination.
Main Methods:
- Generation of a floxed Wnt4 allele with loxP sites.
- Inactivation of Wnt4 using CAGCre and Wnt4(EGFPCre) transgenic mice.
- Analysis of kidney development and embryonic sex determination in Wnt4-deficient models.
Main Results:
- Wnt4 gene inactivation using CAGCre impaired kidney development.
- Wnt4(EGFPCre)-mediated inactivation reduced Wnt4 transcripts and caused severe kidney defects.
- Female embryos with inactivated Wnt4 exhibited partial sex reversal to males.
Conclusions:
- The floxed Wnt4 allele is a valuable tool for investigating Wnt4 signaling throughout the life cycle.
- Wnt4 plays a critical role in kidney development and sexual differentiation.
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