Gain of function of Tbx1 affects pharyngeal and heart development in the mouse

Genesis - Tập 47 Số 3 - Trang 188-195 - 2009
Francesca Vitelli1, Tuong Huynh1, Antonio Baldini1,2,3
1Institute of Biosciences and Technology, Texas A&M University Health Sciences Center, Houston, Texas
2Institute of Genetics and Biophysics, CNR, University Federico II, Naples, Italy
3Telethon Institute of Genetics and Medicine, Naples, Italy

Tóm tắt

AbstractMammalian 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 Tbx1Cre animals to activate expression in the Tbx1‐expression domain. Compound mutant COET;Tbx1Cre/+ 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.

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Genesis

Tập 47 Số 3

188-195

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