Conditional knockout of fibronectin abrogates mouse mammary gland lobuloalveolar differentiation

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2010.07.001 Byline: Keyi Liu, Le Cheng, Andrea Flesken-Nikitin, Lynn Huang, Alexander Y. Nikitin, Bendicht U. Pauli Keywords: Fibronectin; Conditional knockout; Mammary epithelial cell proliferation; Lobuloalveolar differentiation Abstract: Fibronectin (Fn) plays an important part in the branching morphogenesis of salivary gland, lung, and kidney. Here, we examine the effect of the conditional knockout of Fn in the mammary epithelium [Fn.sup.MEp-/-] on postnatal mammary gland development, using Cre-loxP-mediated gene knockout technology. Our data show that Fn deletion causes a moderate retardation in outgrowth and branching of the ductal tree in 5-week-old mice. These defects are partially compensated in virgin 16-week-old mice. However, mammary glands consisting of Fn-deficient epithelial cells fail to undergo normal lobuloalveolar differentiation during pregnancy. The severity of lobuloalveolar impairment ranged from lobular hypoplasia to aplasia in some cases and was associated with the amount of Fn protein recovered from these glands. Decreased rates of mammary epithelial cell proliferation accounted for delayed ductal outgrowth in virgin and lack of alveologenesis in pregnant Fn.sup.MEp-/- mice. Concomitant decreased expression of integrin [beta].sub.1 (Itgb1) and lack of autophosphorylation of focal adhesion kinase (Fak) suggest that this pathology might, at least in part, be mediated by disruption of the Fn/Itgb1/Fak signaling pathway. Article History: Received 13 January 2010; Revised 29 June 2010; Accepted 2 July 2010