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Conditional and constitutive expression of a Tbx1-GFP fusion protein in mice.

Freyer, Laina and Nowotschin, Sonja and Pirity, Melinda K. and Baldini, Antonio and Morrow, Bernice E. (2013) Conditional and constitutive expression of a Tbx1-GFP fusion protein in mice. BMC DEVELOPMENTAL BIOLOGY, 13 (1). p. 33. ISSN 1471-213X

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Abstract

BACKGROUND: Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS) is caused by a 1.5-3 Mb microdeletion of chromosome 22q11.2, frequently referred to as 22q11.2 deletion syndrome (22q11DS). This region includes TBX1, a T-box transcription factor gene that contributes to the etiology of 22q11DS. The requirement for TBX1 in mammalian development is dosage-sensitive, such that loss-of-function (LOF) and gain-of-function (GOF) of TBX1 in both mice and humans results in disease relevant congenital malformations. RESULTS: To further gain insight into the role of Tbx1 in development, we have targeted the Rosa26 locus to generate a new GOF mouse model in which a Tbx1-GFP fusion protein is expressed conditionally using the Cre/LoxP system. Tbx1-GFP expression is driven by the endogenous Rosa26 promoter resulting in ectopic and persistent expression. Tbx1 is pivotal for proper ear and heart development; ectopic activation of Tbx1-GFP in the otic vesicle by Pax2-Cre and Foxg1-Cre represses neurogenesis and produces morphological defects of the inner ear. Overexpression of a single copy of Tbx1-GFP using Tbx1Cre/+ was viable, while overexpression of both copies resulted in neonatal lethality with cardiac outflow tract defects. We have partially rescued inner ear and heart anomalies in Tbx1Cre/- null embryos by expression of Tbx1-GFP. CONCLUSIONS: We have generated a new mouse model to conditionally overexpress a GFP-tagged Tbx1 protein in vivo. This provides a useful tool to investigate in vivo direct downstream targets and protein binding partners of Tbx1.

Item Type: Article
Uncontrolled Keywords: VCFS/DGS, Tbx1, Rosa26, Mouse model, Gain-of-function
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 15 Oct 2013 13:38
Last Modified: 15 Oct 2013 13:38
URI: http://real.mtak.hu/id/eprint/6893

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