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 | |
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 | |
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and production of milk proteins in virgins | Increased spontaneous tumorigenesis in aged mice | [27*] (Moses H, unpublished data) |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*] |