Impaired differentiation and lactational failure ofErbb4-deficient mammary glands identify ERBB4 as an obligate mediator of STAT5

• DOI: 10.1242/dev.00715
• Publication Date: 2003-09-09T02:20:58Z
• Authors: Weiwen Long; Kay-Uwe Wagner; K. C. Kent Lloyd; Nadine Binart; Jonathan M. Shill...; Lothar Hennighausen; Frank E. Jones
• Keywords: STAT5; ERBB4; ErbB

The ERBB family of type 1 receptor tyrosine kinases and their ligands have crucial functions during mammopoiesis, but the signaling networks that ultimately regulate activity in breast remained elusive. Here, we show mice with Cre-lox mediated deletions both Erbb4 alleles within developing mammary gland (Erbb4(Flox/Flox)Wap-Cre) fail to accumulate lobuloalveoli or successfully engage lactation at parturition owing, part, impaired epithelial proliferation. Analysis differentiation factor STAT5 by immunohistochemistry western blot revealed a complete ablation activation Erbb4(Flox/Flox)Wap-Cre epithelium parturition. Consistent disrupted function, glands failed express marker NPT2B. Defects functional were accompanied profound reduction expression STAT5-regulated milk genes casein beta whey acidic protein. We propose ERBB4 as an essential mediator signaling, loss contributes observed containing conditional deletions.