Tissue-specific expression of Cre recombinase from the Tgfb3 locus.
Tgfb3, a member of the TGF-beta superfamily, is tightly regulated, both spatially and temporally, during embryogenesis. Previous mouse knockout studies have demonstrated that Tgfb3 is absolutely required for normal palatal fusion and pulmonary development. We have generated a novel tool to ablate genes in Tgfb3-expressing cells by targeting the promoterless Cre-pgk-Neo cassette into exon 1 of the mouse Tgfb3 gene, which generates a functionally null Tgfb3 allele. Using the Rosa26 reporter assay, we demonstrate that Cre-induced recombination was already induced at embryonal day 10 (E10) in the ventricular myocardium, limb buds, and otic vesicles. At E14, robust recombination was detected in the prefusion palatal epithelium. Deletion of the TGF-beta type I receptor Alk5 (Tgfbr1) specifically in Tgfb3 expressing cells using the Tgfb3-Cre driver line lead to a cleft palate phenotype similar to that seen in conventional Tgfb3 null mutants. In addition, Alk5/ Tgfb3-Cre mice displayed hydrocephalus, and severe intracranial bleeding due to germinal matrix hemorrhage.
Yang
Liang-Tung
LT
Developmental Biology Program, The Saban Research Institute of Childrens Hospital Los Angeles, Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90027, USA.
Li
Wai-Yee
WY
Kaartinen
Vesa
V
D000818:Animals; D002972:Cleft Palate / Q000196:embryology; D005821:Genetic Techniques; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010159:Palate / Q000196:embryology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000235:genetics* / Q000378:metabolism
D018125:Receptors, Transforming Growth Factor beta; C509045:Tgfb3 protein, mouse; D053782:Transforming Growth Factor beta3; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625842:Tgfbr1 protein, mouse; C045073:Cre recombinase; D019426:Integrases