[CITATION][C] Conditional inactivation of the TGF‐β type II receptor using Cre: Lox

A Chytil, MA Magnuson, CVE Wright, HL Moses - genesis, 2002 - Wiley Online Library
A Chytil, MA Magnuson, CVE Wright, HL Moses
genesis, 2002Wiley Online Library
There is solid evidence that the TGF-β superfamily plays an important role in mammalian
development. A great deal of the evidence comes from targeted gene inactivation in mice.
For example, disruption of Smad2 and Smad4 results in perigastrulation lethality in mice
(Weinstein et al., 1998; Sirard et al., 1998). Animals lacking Smad5 die between E9–11.5
because of embryonic and extraembryonic defects (Chang et al., 1999). Interestingly, mice
deficient in the type II TGF-β receptor (TβRII) die at 10.5 dpc with similar defects in …
There is solid evidence that the TGF-β superfamily plays an important role in mammalian development. A great deal of the evidence comes from targeted gene inactivation in mice. For example, disruption of Smad2 and Smad4 results in perigastrulation lethality in mice (Weinstein et al., 1998; Sirard et al., 1998). Animals lacking Smad5 die between E9–11.5 because of embryonic and extraembryonic defects (Chang et al., 1999). Interestingly, mice deficient in the type II TGF-β receptor (TβRII) die at 10.5 dpc with similar defects in hematopoiesis and vasculogenesis (Oshima et al., 1996), suggesting that there may be cross-talk between BMP and TGF-β signaling.
Furthermore, there is compelling evidence indicating that the TGF-β signaling pathway is tumor suppressive. Much of this evidence is derived from studies demonstrating inactivating mutations in human tumors of genes involved in TGF-β signal transduction, including DPC4/Smad4, Smad2, and the TβRII (Derynck and Akhurst, 2001). Decreased TβRII expression in the absence of detectable mutations has also been reported to be common in premalignant legions (Gobbi et al., 1999). Additional evidence for a tumor suppressor role for the TGF-β signaling pathway was derived from studies with genetically modified mice. Overexpression of TGF-β1 in mammary epithelial cells suppresses the development of carcinomas (Pierce et al., 1995). Expression of a dominant negative type II TGF-β receptor (DNIIR) in mammary epithelial cells increases the incidence of mammary carcinomas (Gorska and Moses, unpublished observation).
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