The removal of the Wt1 according to an article published in the journal PLOS genetics and directed by the lecturer Ofelia Martínez-Estrada, from the Faculty of Biology and the Institute for Research in Biomedicine (IRBio) of the University of Barcelona.
Among the contributors to the article are experts Francesc X. Soriano, from the Department of Cell Biology, Physiology and Immunology, and the Institute of Neurosciences at UB (UBNeuro), and Manuel Reina, from the same department and from the group of research Celltec UB.
A decisive gene in the biology of sex
The Wt1 or Wilms tumor gene is expressed during mammalian embryonic development in many organs and tissues (urogenital system, spleen, heart, diaphragm, etc.). In the scientific literature, mutations in the Wt1 gene are linked to certain pathologies – syndromes such as Denys-Drash, Frasier and Meacham – which include genitourinary malformations and differences in sexual development (such as ambiguous genitalia or a abnormal development of the gonads).
These differences in sex development are congenital disorders in which the development of the chromosomal, gonadal, or anatomical sex is atypical. Despite efforts to understand the genetic factors behind these alterations, the origin is unknown in many cases and it is difficult to offer an accurate diagnosis to those affected.
Mouse models presenting modifications in the expression of key genes of sexual development appear as decisive elements for the study of this complex process in mammals. Thus, in recent years, new genetic tools have been generated in mutant mouse models to study different aspects of the biology of the WT1 embarrassed.
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 findings, women and men Wt1KO the mutant mice – unable to express the Wt1 gene in the reproductive organs from the earliest stages of formation – showed ambiguous genital tracts and their gonads remained at an indifferent stage.
“In this study, we claim that the Wt1 is necessary to activate the pathways that determine the development of the male and female sex, since the mutant embryonic gonads do not express the specific genes of each genetic program”, notes Professor Ofelia Martínez-Estrada, from the Department of Cell Biology, Physiology and Immunology of BU.
So far, it has been difficult to assess the functions of WT1 transcription factor – encoded by the mentioned gene – during early gonad differentiation and its impact on adult sexual development. The absence of development in the gonads or in the genital tract (gonadal agenesis) and the embryonic lethality shown in Wt1KO mutant mice have hampered progress in research to elucidate the role of this gene in these developmental processes.
“Based on the results obtained, we propose that this mouse model may contribute to improving knowledge about the functions of the WT1 gene in certain populations of progenitor cells in different organs and tissues, as well as the importance of these cell populations in the formation of organs in adults,” concludes speaker Ofelia Martínez-Estrada.
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