The role of Wt1 in Müllerian duct development

<p>WT1 is a zinc finger transcription factor widely expressed in the urogenital system. Human mutations of <em>WT1</em> lead to pediatric nephroblastoma as well as frequent differences of sex development (DSDs). Previous studies have suggested that WT1 acts as an activator for <em>Amhr2</em>, 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 <em>Wt1</em> in the Müllerian duct (MD) mesenchyme using a novel conditional null reporter allele, <em>Wt1 flox-RFP</em>. This allele utilizes the Cre-lox system to delete exons 8 and 9 of <em>Wt1</em>, 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 <em>Wt1 </em>deletion in the MD mesenchyme using <em>Amhr2-Cre</em>. We found that loss of WT1 function in the MD mesenchyme resulted in the male developing a uterus. This is the first <em>in vivo</em> demonstration that <em>Wt1</em> has a role in MD regression within the MD mesenchyme.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2024

Authors dc:creator

• Aloway, Jace
• <p>https://orcid.org/0000-0001-5430-5799</p>

Contributors dc:contributor

• Dr. Richard Behringer
• Dr. Vicki Huff
• Dr. George Eisenhoffer

• Wt1
• development
• genetics
• uterus
• oviduct
• DSD
• Amhr2
• Mullerian duct
• Animal Experimentation and Research
• Developmental Biology

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1397

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2454