Molecular characterization of Wdr13 knockout female mice uteri: a model for human endometrial hyperplasia
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Date
2020
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Abstract
Endometrial hyperplasia (EH) is a condition where uterine endometrial glands show excessive
proliferation of epithelial cells that may subsequently progress into endometrial cancer (EC). Modern
lifestyle disorders such as obesity, hormonal changes and hyperinsulinemia are known risk factors for
EH. A mouse strain that mimics most of these risk factors would be an ideal model to study the stage wise progression of EH disease and develop suitable treatment strategies. Wdr13, an X-linked gene, is
evolutionarily conserved and expressed in several tissues including uteri. In the present study, Wdr13
knockout female mice developed benign proliferative epithelium that progressed into EH at around
one year of age accompanied by an increase in body weight and elevated estradiol levels. Molecular
characterization studies revealed increase in ERα, PI3K and a decrease in PAX2 and ERβ proteins in
Wdr13 mutant mice uteri. Further, a decrease in the mRNA levels of cell cycle inhibitors, namely; p21
and cyclin G2 was seen. Leukocyte infltration was observed in the uterine tissue of knockout mice at
around 12 months of age. These physiological, molecular and pathological patterns were similar to
those routinely seen in human EH disease and demonstrated the importance of WDR13 in mice uterine
tissue. Thus, the genetic loss of Wdr13 in these mice led to mimicking of the human EH associated
metabolic disorders making Wdr13 knockout female mice a potential animal model to study human
endometrial hyperplasia.