The role of Wt1 in Müllerian duct development

WT1 is a zinc finger transcription factor widely expressed in the urogenital system. Human mutations of WT1 lead to pediatric nephroblastoma as well as frequent differences of sex development (DSDs). Previous studies have suggested that WT1 acts as an activator for Amhr2, a necessary component of typical male differentiation. We used the mouse as a model to investigate the role of WT1 in sex development, where we deleted Wt1 in the Müllerian duct (MD) mesenchyme using a novel conditional null reporter allele, Wt1 flox-RFP. This allele utilizes the Cre-lox system to delete exons 8 and 9 of Wt1, disrupting the DNA binding capability of the protein. Simultaneously, a nuclear red fluorescent protein is activated in cells expressing the recombined allele. After validating and characterizing this allele, we drove Wt1 deletion in the MD mesenchyme using Amhr2-Cre. We found that loss of WT1 function in the MD mesenchyme resulted in the male developing a uterus. This is the first in vivo demonstration that Wt1 has a role in MD regression within the MD mesenchyme.