Generation of mice carrying a knockout-first and conditional-ready allele of transforming growth factor beta2 gene.

ABSTRACT: Transforming growth factor beta2 (TGF?2) is a multifunctional protein which is expressed in several embryonic and adult organs. TGFB2 mutations can cause Loeys Dietz syndrome, and its dysregulation is involved in cardiovascular, skeletal, ocular, and neuromuscular diseases, osteoarthritis, tissue fibrosis, and various forms of cancer. TGF?2 is involved in cell growth, apoptosis, cell migration, cell differentiation, cell-matrix remodeling, epithelial-mesenchymal transition, and wound healing in a highly context-dependent and tissue-specific manner. Tgfb2(-/-) mice die perinatally from congenital heart disease, precluding functional studies in adults. Here, we have generated mice harboring Tgfb2(?geo) (knockout-first lacZ-tagged insertion) gene-trap allele and Tgfb2(flox) conditional allele. Tgfb2(?geo/?geo) or Tgfb2(?geo/-) mice died at perinatal stage from the same congenital heart defects as Tgfb2(-/-) mice. ?-galactosidase staining successfully detected Tgfb2 expression in the heterozygous Tgfb2(?geo) fetal tissue sections. Tgfb2(flox) mice were produced by crossing the Tgfb2(+/?geo) mice with the FLPeR mice. Tgfb2(flox/-) mice were viable. Tgfb2 conditional knockout (Tgfb2(cko/-) ) fetuses were generated by crossing of Tgfb2(flox/-) mice with Tgfb2(+/-) ; EIIaCre mice. Systemic Tgfb2(cko/-) embryos developed cardiac defects which resembled the Tgfb2(?geo/?geo) , Tgfb2(?geo/-) , and Tgfb2(-/-) fetuses. In conclusion, Tgfb2(?geo) and Tgfb2(flox) mice are novel mouse strains which will be useful for investigating the tissue specific expression and function of TGF?2 in embryonic development, adult organs, and disease pathogenesis and cancer. genesis

SUBMITTER: Ishtiaq Ahmed AS 

PROVIDER: S-EPMC4270118 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature