Anatomical studies of the mouse genital tubercle.

Background: To study the etiology of hypospadias, we propose the use of a mouse model, the embryonic mouse genital tubercle. In this study, we define the development of the mouse genital tubercle with special emphasis on urethral formation demonstrating anatomical similarities to human development.

Materials And Methods: Serial sections of genital tubercles from embryonic male and female mice ages 14 to 21 days gestation from timed pregnant animals, newborn and adult mice were immunohistochemical stained with antibodies to E-cadherin, cytokeratins 7, 10, and 14. Patency of the urethral was assessed by india ink injection via the bladder. Urethral lumen morphology was determined by the creation of plastic resin cast. Surface morphology of the genital tubercle was defined by scanning electron microscopy.

Results: India Ink injection into the bladder showed that the urethral lumen was patent from 14 days gestation. Plastic resin casts revealed that the male urethra was characterized by a S shaped curve, the presence of the bulbar urethral gland and a longer length than age matched females. The ontogeny of the genital tubercle development revealed two epithelial edges that subsequently touched and fused into the completed urethra. During development cytokeratin immunohistochemical staining demonstrated that the epithelial cells of the urethral lumen are of bladder origin and the surface cells of skin origin.

Conclusion: The functional and developmental anatomy of the mouse genital tubercle provides a useful model to study normal and abnormal human urethral development.