Biogenesis and function of mouse mammary epithelium depends on the presence of functional alpha-catenin.

Alpha-catenin is a structural molecule and essential to the function of epithelial adherens junctions. Its role in the morphogenesis of mammary epithelium was explored using experimental mouse genetics. Since loss of alpha-catenin in mice leads to embryonic lethality, the alpha-catenin gene was flanked by loxP sites and inactivated in mammary epithelium using the WAP-Cre and MMTV-Cre transgenes. Loss of alpha-catenin arrested alveolar epithelial expansion. These cells lacked proper polarity and markers of functional differentiation, which resulted in impaired milk protein gene expression. Without alpha-catenin, increased epithelial cell death was observed at parturition and the tissue resembled an involuted gland that is normally observed after weaning. Lastly, no tumors were detected in mammary tissue lacking alpha-catenin.

Involvement of nitric oxide and the ovarian blood follicle barrier in murine follicular cyst development.

OBJECTIVE: To test the involvement of nitric oxide in murine ovarian follicular cysts. DESIGN: Controlled animal study. SETTING: Academic research environment. ANIMAL(S): Immature female B6D2F1 mice at 23 +/- 2 days old. Ovarian cysts were induced by implanting miniosmotic pumps that delivered and maintained constant levels of hCG. Nitric oxide studies included the delivery of nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine methyl ester (L-NAME), or N(G)-nitro-D-arginine methyl ester, by the same method. Ovulation assays measured cumulus oocyte complexes and blood follicle barrier (BFB) function. RESULT(S): Chronic treatment with hCG induced enlarged ovaries containing multiple follicular cysts, which were approximately double the size of follicles in sham-operated mice. These cysts enclosed few, if any granulosa cells, secreted high levels of testosterone, and had impaired ovarian BFB function. Inhibition of NOS by L-NAME during ovarian cyst formation reduced the size of follicular cysts, sustained normal testosterone levels, and maintained hormonal BFB reactivity in cystic follicles. CONCLUSION(S): Nitric oxide was found to be involved in the formation of hCG-induced murine follicular cysts and complications associated with these cysts were ameliorated by the NOS inhibitor L-NAME.