Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge Syndrome

The patients with DiGeorge syndrome (DGS), caused by deletion containing dozens of genes in chromosome 22, often carry cardiovascular problem and hearing loss associated with chronic otitis media. Inside the deletion region, a transcription factor TBX1 was highly suspected. Furthermore, similar DGS...

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Main Authors: Jiaofeng Chen, Xue Zhang, Jie Li, Chenmeng Song, Yichang Jia, Wei Xiong
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2016/5836143
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author Jiaofeng Chen
Xue Zhang
Jie Li
Chenmeng Song
Yichang Jia
Wei Xiong
author_facet Jiaofeng Chen
Xue Zhang
Jie Li
Chenmeng Song
Yichang Jia
Wei Xiong
author_sort Jiaofeng Chen
collection DOAJ
description The patients with DiGeorge syndrome (DGS), caused by deletion containing dozens of genes in chromosome 22, often carry cardiovascular problem and hearing loss associated with chronic otitis media. Inside the deletion region, a transcription factor TBX1 was highly suspected. Furthermore, similar DGS phenotypes were found in the Tbx1 heterozygous knockout mice. Using ENU-induced mutagenesis and G1 dominant screening strategy, here we identified a nonsynonymous mutation p.W118R in T-box of TBX1, the DNA binding domain for transcription activity. The mutant mice showed deficiency of inner ear functions, including head tossing and circling, plus increased hearing threshold determined by audiometry. Therefore, our result further confirms the pathogenic basis of Tbx1 in DGS, points out the crucial role of DNA binding activity of TBX1 for the ear function, and provides additional animal model for studying the DGS disease mechanisms.
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spelling doaj-art-dc2b959958474ad0bbaecfbbadff4b8f2025-08-20T02:21:35ZengWileyNeural Plasticity2090-59041687-54432016-01-01201610.1155/2016/58361435836143Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge SyndromeJiaofeng Chen0Xue Zhang1Jie Li2Chenmeng Song3Yichang Jia4Wei Xiong5School of Life Sciences, Tsinghua University, Beijing, ChinaSchool of Medicine, Tsinghua University, Beijing, ChinaSchool of Life Sciences, Tsinghua University, Beijing, ChinaSchool of Life Sciences, Tsinghua University, Beijing, ChinaSchool of Medicine, Tsinghua University, Beijing, ChinaSchool of Life Sciences, Tsinghua University, Beijing, ChinaThe patients with DiGeorge syndrome (DGS), caused by deletion containing dozens of genes in chromosome 22, often carry cardiovascular problem and hearing loss associated with chronic otitis media. Inside the deletion region, a transcription factor TBX1 was highly suspected. Furthermore, similar DGS phenotypes were found in the Tbx1 heterozygous knockout mice. Using ENU-induced mutagenesis and G1 dominant screening strategy, here we identified a nonsynonymous mutation p.W118R in T-box of TBX1, the DNA binding domain for transcription activity. The mutant mice showed deficiency of inner ear functions, including head tossing and circling, plus increased hearing threshold determined by audiometry. Therefore, our result further confirms the pathogenic basis of Tbx1 in DGS, points out the crucial role of DNA binding activity of TBX1 for the ear function, and provides additional animal model for studying the DGS disease mechanisms.http://dx.doi.org/10.1155/2016/5836143
spellingShingle Jiaofeng Chen
Xue Zhang
Jie Li
Chenmeng Song
Yichang Jia
Wei Xiong
Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge Syndrome
Neural Plasticity
title Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge Syndrome
title_full Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge Syndrome
title_fullStr Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge Syndrome
title_full_unstemmed Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge Syndrome
title_short Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge Syndrome
title_sort identification of a novel enu induced mutation in mouse tbx1 linked to human digeorge syndrome
url http://dx.doi.org/10.1155/2016/5836143
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