Adult < i > Gli2+/ – < /i > ; < i > Gli3 Δ699/+ < /i > Male and Female Mice Display a Spectrum of Genital Malformation

by Fei He, Pedram Akbari, Rong Mo, Jennifer J. Zhang, Chi-Chung Hui, Peter C. Kim, Walid A. Farhat Disorders of sexual development (DSD) encompass a broad spectrum of urogenital malformations and are amongst the most common congenital birth defects. Although key genetic factors such as the hedgehog (Hh) family have been identified, a unifying postnatally viable model displaying the spectrum of male and female urogenital malformations has not yet been reported. Since human cases are diagnosed and treated at various stages postnatally, equivalent mouse models enabling analysis at similar stages are of significant interest. Additionally, all non-Hh based genetic models investigating DSD disp lay normal females, leaving female urogenital development largely unknown. Here, we generated compound mutant mice,Gli2+/ –;Gli3Δ699/+, which exhibit a spectrum of urogenital malformations in both males and females upon birth, and also carried them well into adulthood. Analysis of embryonic day (E)18.5 and adult mice revealed shortened anogenital distance (AGD), open ventral urethral groove, incomplete fusion of scrotal sac, abnormal penile size and structure, and incomplete testicular descent with hypoplasia in male mice, whereas female mutant mice displayed reduced AGD, urinary incontinence, and a number of uterine anomalies such as vaginal duplication. Male and female fertility was also investigated via breeding cages, and it was identified that male mice were infertile while females ...
Source: PLoS One - Category: Biomedical Science Authors: Source Type: research