Generation of mice carrying a knockout‐first and conditional‐ready allele of transforming growth factor beta2 gene. Issue 9 (9th June 2014)

• Record Type: Journal Article
• Authors: Ishtiaq Ahmed, A. S.; Bose, Gracelyn C.; Huang, Li; Azhar, Mohamad
• Is Part Of: Genesis. Volume 52:Issue 9(2014:Sep.)
• Page Start: 817
• Page End: 826
• Publication Date: 2014-06-09
• Subjects: Developmental genetics -- Periodicals; Genetics -- Periodicals; Developmental biology -- Periodicals; Embryology -- Periodicals; Genetic regulation -- Periodicals; 576.5
• DOI: 10.1002/dvg.22795
• Languages: English
• ISSNs: 1526-954X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Transforming growth factor beta2 (TGFβ2) is a multifunctional protein which is expressed in several embryonic and adult organs. <italic>TGFB2</italic> 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. TGFβ2 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. <italic>Tgfb2</italic><sup>−/−</sup> mice die perinatally from congenital heart disease, precluding functional studies in adults. Here, we have generated mice harboring <italic>Tgfb2</italic><sup>βgeo</sup> (knockout‐first <italic>lacZ</italic>‐tagged insertion) gene‐trap allele and <italic>Tgfb2</italic><sup>flox</sup> conditional allele<italic>. Tgfb2</italic><sup>βgeo/βgeo</sup> or <italic>Tgfb2</italic><sup>βgeo/‐</sup> mice died at perinatal stage from the same congenital heart defects as <italic>Tgfb2</italic><sup>−/−</sup> mice. β‐galactosidase staining successfully detected <italic>Tgfb2</italic> expression in the heterozygous <italic>Tgfb2</italic><sup>βgeo</sup> fetal tissue sections. <italic>Tgfb2</italic><sup>flox</sup> mice were produced by crossing the <italic>Tgfb2</italic><sup>+/βgeo</sup> mice with the FLPeR mice. <italic>Tgfb2</italic><sup>flox/−</sup> mice were viable. <italic>Tgfb2</italic> conditional knockout (<italic>Tgfb2</italic><sup>cko/−</sup>) fetuses were generated by crossing of <italic>Tgfb2</italic><sup>flox/−</sup> mice with <italic>Tgfb2</italic><sup>+/−</sup>; <italic>EIIaCre</italic> mice. Systemic <italic>Tgfb2</italic><sup>cko/−</sup> embryos developed cardiac defects which resembled the <italic>Tgfb2</italic><sup>βgeo/βgeo</sup>, <italic>Tgfb2</italic><sup>βgeo/−</sup>, and <italic>Tgfb2</italic><sup>−/−</sup> fetuses. In conclusion, <italic>Tgfb2</italic><sup>βgeo</sup> and <italic>Tgfb2</italic><sup>flox</sup> mice are novel mouse strains which will be useful for investigating the tissue specific expression and function of TGFβ2 in embryonic development, adult organs, and disease pathogenesis and cancer. genesis 52:817–826, 2014. © 2014 Wiley Periodicals, Inc.</p> </abstract>