Mice overexpressing genes from the 22q11 region deleted in velo-cardio-facial syndrome/DiGeorge syndrome have middle and inner ear defects

作者: Birgit Funke , JonathanA Epstein , LazarosK Kochilas , MinMin Lu , RajK Pandita

DOI: 10.1093/HMG/10.22.2549

关键词:

摘要: Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS) is a congenital anomaly disorder associated with hemizygous 22q11 deletions. We previously showed that bacterial artificial chromosome (BAC) transgenic mice overexpressing four transgenes, PNUTL1, (CDCrel-1), GP1B beta, TBX1 and WDR14, had reduced viability, cardiovascular malformations thymus gland hypoplasia. Since these are hallmark features of VCFS/DGS, we analyzed the for additional anomalies. found have important defects in middle inner ear directly relevant to disorder. The most striking defect was presence chronic otitis media, common finding VCFS/DGS patients. In addition, hyperactive circling behavior sensorineural hearing loss. This malformations, analogous Mondini dysplasia humans reported occur propose overexpression one or more transgenes responsible etiology mice. Based upon its pattern expression functional studies gene, TbX1 likely plays central role. Haploinsufficiency may be disorders

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