Differential mammary morphogenesis along the anteroposterior axis in Hoxc6gene targeted mice

Mammary epithelial cell proliferation, branching, and differentiation span from the appearance of the mammary bud in midgestation through to the cycli ng mammary gland in adulthood, Here, we show that females homozygous for a targeted disruption of the Hoxc6 homeobox gene produce thoracic mammary gla nds that are slightly under-developed at birth and completely cleared of ep ithelium by adulthood, and inguinal mammary ducts that are dilated and fail to regress in response to ovariectomy, Mammary buds are detected in E12.5 Hoxc6 homozygous embryos. However, in newborn Hoxc6 homozygous females, bra nching ductal structures and fat pad development are reduced. Whole-mount a nd histologic analyses of mammary glands from adult Hoxc6 homozygous female s show the absence of mammary epithelium in thoracic glands and dilated duc ts in inguinal glands at 100% penetrance. Histologic analysis of inguinal m ammary glands from ovariectomized Hoxc6 homozygous females demonstrates no signs of the expected regression of epithelium, suggesting that these gland s are not responsive to the loss of ovarian hormone signals, We further obs erve repression of Hoxc6 expression specifically within mammary stroma by e strogen and progesterone. Hoxc6 homozygous mice also exhibit a homeotic tra nsformation of the second thoracic vertebra into the first (T2 to T1 conver sion with 60% penetrance), corresponding to both the gene's anterior bounda ry of expression and the most extreme appearance of mammary defects. The po sition-specific phenotypes observed and the potential role for Hoxc6 in med iating hormone-regulated ductal expansion and regression in the adult femal e are discussed. (C) 2000 Wiley-Liss, Inc.