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Gain of function of Tbx1 affects pharyngeal and heart development in the mouse
Author(s) -
Vitelli Francesca,
Huynh Tuong,
Baldini Antonio
Publication year - 2009
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20476
Subject(s) - tbx1 , transgene , phenotype , mutant , biology , ectopic expression , gene , genetically modified mouse , wild type , loss function , gene expression , function (biology) , microbiology and biotechnology , genetics , promoter
Mammalian development is highly sensitive to Tbx1 gene dosage reduction. Gene function insights can also be learned from increased or ectopic expression. The authors generated a novel mouse transgenic line, named COET, which expresses Tbx1 upon Cre‐mediated recombination. The authors crossed this transgenic line with Tbx1 Cre animals to activate expression in the Tbx1 ‐expression domain. Compound mutant COET; Tbx1 Cre /+ animals died after birth and showed heart enlargement. At E18.5, compound mutants showed ventricular septal defects and thymic abnormalities. The authors crossed compound mutants into a Tbx1 null background to understand whether this phenotype is caused by gene overdosage. Results showed that gene dosage reduction at the endogenous locus could not rescue heart and thymic defects, although the transgene rescued the loss of function phenotype. Thus, the transgenic phenotype appears to be due to gain of function. Resultant data demonstrate that Tbx1 expression must be tightly regulated to be compatible with normal embryonic development. genesis 47:188–195, 2009. © 2009 Wiley‐Liss, Inc.