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Table 1 Transgenic mouse models designed to address the roles of TGF-βs in the mammary gland

From: Transforming growth factor-β and breast cancer: Lessons learned from genetically altered mouse models

Gain-of-functionmodels      
Model Transgene Expression pattern Developmental phenotype Tumor phenotype References
MMTV-TGF-β1 S223/225 Constitutively activated form of TGF-β1 Mammary epithelium Decreased ductal development in young animals Inhibition of tumorigenesis induced by chemical carcinogens or oncogenes [8*,11**]
WAP-TGF-β1 S223/225 Constitutively activated form of TGF-β1 Mammary epithelium, specifically in lobulo alveolar progenitors and fate-committed daughters Inability to lactate due to decreased maintenance of lobuloalveolar structures Inhibition of tumorigenesis induced by TGF-β [7,9*] (Smith G, unpublished data)
Loss-of-function models      
MMTV-DNR Dominant-negative mutant type II TGF-β receptor Mammary epithelium Precocious lobuloalveolar development and production of milk proteins in virgins Increased spontaneous tumorigenesis in aged mice [27*] (Moses H, unpublished data)
MMTV-DNR Dominant-negative mutant type II TGF-β receptor Mammary epithelium Increased lobuloalveolar development in virgins Increased tumorigenesis in response to carcinogens [28**]
MT-DNR Dominant-negative mutant type II TGF-β receptor Mammary stroma Increased ductal branching Not described [29*]
  1. DNR, dominant-negative mutant type II transforming growth factor-β receptor; MMTV, mouse mammary tumor virus; WAP, whey acidic protein; MT, metallothionein promoter; TGF, transforming growth factor.