Spontaneous mutation in mice provides new insight into the genetic mechanisms that pattern the seminal vesicles and prostate gland

The seminal vesicles and prostate gland are anatomically adjacent male sex-accessory glands. Although they arise from different embryonic precursor structures and express distinct sets of secretory proteins, these organs share common features in their developmental biology. A key shared developmental feature is the elaboration of complex secretory epithelia with tremendous surface area from simple precursor structures with juxtaposed epithelial and mesenchymal cells. In this study, new insight into the nature of the biological processes that underlie glandular morphogenesis is achieved by analyzing the phenotypes present in mice that harbor a spontaneous mutation, seminal vesicle shape (svs), previously identified for causing altered seminal vesicle morphology in adults. An examination of seminal vesicle development in svs mice provides the first evidence that the concurrent processes of epithelial branching and epithelial infolding are distinct processes under separate genetic control. It also provides the first direct evidence that the thickness and topology of the smooth muscle layer in the seminal vesicles are determined by interaction with the glandular epithelium during the branching process. In addition, the seminal vesicle phenotype in svs mice is shown to phenocopy the morphologic form present in certain other mammals such as the guinea pig, raising the possibility that the svs mutation is the sort of variant that arises during evolution. By also including an investigation of the prostate gland, this study also identifies previously unrecognized phenotypes in svs prostates, including increased gland size and dramatically reduced levels of branching morphogenesis. Finally, this study advances the goal of identifying the svs gene by mapping the svs mutation relative to known molecular markers and testing Fgfr2 as a candidate gene. The finding that the svs mutation maps to a genomic region syntenic to a region frequently deleted in human prostate tumors, together with the prostatic phenotype present in svs mice, further raises the interesting possibility that the svs mutation will identify a candidate prostate tumor suppressor gene.