MALE ACCESSORY SEX-ORGAN MORPHOGENESIS IS ALTERED BY LOSS OF FUNCTIONOF HOXD-13

The role of the Hox gene Hoxd-13 in postnatal morphogenesis of the mal e accessory sex organs was examined by correlating the distribution an d temporal regulation of expression in the accessory sex organs of pos tnatal mice with morphologic abnormalities of Hoxd-13-deficient transg enic mice. Previous studies of Hoxd-13 expression in the perinatal per iod have shown a broad domain of expression in the lower genitourinary tract, with expression in both mesenchyme and epithelium; focal expre ssion was also noted in the epithelium of the nascent ducts of the dev eloping prostate. Quantitative RT-PCR studies of Hoxd-13 expression in the 5 day mouse confirm widespread expression in the accessory sex or gans developing from both the Wolffian duct and the urogenital sinus. Expression is downregulated with age, and a detailed time course of ex pression in the developing prostate shows that the level of Hoxd-13 ex pression correlates with morphogenetic activity in the development of the prostate ductal system. Transgenic Hoxd-13-deficient mice display multiple abnormalities in the male accessory sex organs, The most seve re abnormalities were observed in organs exhibiting ductal branching d uring postnatal development and included diminished mesenchymal foldin g in the seminal vesicles, decreased size and diminished ductal branch ing in the ventral and dorsal prostate, and agenesis of the bulboureth ral gland. We conclude that Hoxd-13 expression in the postnatal period correlates with a period of intense morphogenetic activity in accesso ry sex organ development and that the function of Hoxd-13 is evidenced by morphologic abnormalities in accessory sex organs of the Hoxd-13-d eficient mutant. (C) 1997 Wiley-Liss, Inc.