The deletion of the Wt1 gene during the early stages of the embryonic reproductive organ formation leads to differences in sex development in adult mice, according to an article published in the journal PLOS Genetics and led by the lecturer Ofelia Martínez-Estrada, from Institut de Briomedicina de la UB (IBUB), of Faculty of Biology.
Among the participants in the article are Francesc X. Soriano, from Institute of Neurosciences of the UB (UBNeuro), and Manuel Reina, from Research Group Celltec UB.
A decisive gene in the biology of sex
The Wt1 gene or Wilms tumour gene is expressed during the embryonic development of mammals in many organs and tissues (urogenital system, spleen, heart, diaphragm, etc.). In scientific literature, the mutations of the Wt1 gene are related to some pathologies —syndromes such as Denys-Drash, Frasier and Meacham’s— which include genitourinary defects and differences in the sex development (such as ambiguous genitalia or abnormal development of the gonads).
These differences in the sexual development are congenital disorders in which the development of the chromosomal, gonadal or anatomic sex is atypical. Despite the efforts to understand the genetic factors that cause these alterations, the origin is unknown in many cases and it is hard to offer a precise diagnosis to the affected people.
Murine models with modifications in the expression of key genes in the sex development are shaped as decisive elements for studying this complex process in mammals. Therefore, in recent years, new genetic tools have been generated in mutant mice models to study different aspects of the biology of the WT1 gene.
As part of the study, the team presents a new genetically modified mouse model (Wt1KO) which revealed the importance of the Wt1 gene in the initial differentiation of the embryonic gonad at early stages and its impact in the formation of the reproductive system of adult mice. According to the conclusions, female and male Wt1KO mutant mice —unable to express the Wt1 gene in reproductive organs from the early formation stages– showed ambiguous genital tracts and their gonads remained at an undifferenced stage.
Reference article:
Torres-Cano, A.; Portella-Fortuny, R.; Müller-Sánchez, C.; Porras-Marfil, S.; Ramiro-Pareta, M.; Chau, Y.; Reina, M.; Soriano, F. X; Martínez-Estrada, O. «Deletion of Wt1 during early gonadogenesis leads to differences of sex development in male and female adult mice». PLOS Genetics, June 2022. DOI: 10.1371/journal.pgen.1010240
