Genetic background has a major effect on the penetrance and severity of craniofacial defects in mice hetelrozygous for the gene encoding the nucleolar protein treacle
Genetic background has a major effect on the penetrance and severity of craniofacial defects in mice hetelrozygous for the gene encoding the nucleolar protein treacle
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DOI：
10.1002/dvdy.20004
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发表时间：
2004-04-01
影响因子：
2.5
通讯作者：
Dixon, MJ
中科院分区：
文献类型：
--
作者：
Dixon, J;Dixon, MJ
Treacher Collins综合征（TCS）是一种颅面疾病，由编码核仁蛋白糖浆的TCOF1突变引起。临床特征的严重程度差异很大，包括下颌骨发育不全、外耳和中耳小骨异常以及腭裂。为了确定Treacle的体内功能，我们之前在C57BL/6和129混合背景下产生了Tcof1杂合小鼠。这些小鼠表现出致命的表型，包括上颌骨发育异常，眼睛和鼻腔缺失以及神经管缺陷。在这里，我们表明，将突变放置在不同的遗传背景上，对颅面和其他缺陷的外显率和严重程度有重大影响。后代表现出明显不同的菌株依赖表型，从混合CBA/Ca和129背景下的极度严重和致死，到混合BALB/c和129背景下的明显正常和存活。在前一种情况下，除了非常严重的颅面表型外，cba衍生的杂合小鼠还表现出长骨延迟骨化，肋骨融合和手指异常。我们的研究结果表明，不同遗传背景的因素对Tcof1表型有广泛的影响。发展(C) 2004 Wiley-Liss, Inc。
Treacher Collins syndrome (TCS) is a craniofacial disorder that results from mutations in TCOF1, which encodes the nucleolar protein Treacle. The severity of the clinical features exhibits wide variation and includes hypoplasia of the mandible and maxilla, abnormalities of the external ears and middle ear ossicles, and cleft palate. To determine the in vivo function of Treacle, we previously generated Tcof1 heterozygous mice on a mixed C57BL/6 and 129 background. These mice exhibited a lethal phenotype, which included abnormal development of the maxilla, absence of the eyes and nasal passages, and neural tube defects. Here, we show that placing the mutation onto different genetic backgrounds has a major effect on the penetrance and severity of the craniofacial and other defects. The offspring exhibit markedly variable strain-dependent phenotypes that range from extremely severe and lethal in a mixed CBA/Ca and 129 background, to apparently normal and viable in a mixed BALB/c and 129 background. In the former case, in addition to a profoundly severe craniofacial phenotype, CBA-derived heterozygous mice also exhibited delayed ossification of the long bones, rib fusions, and digit anomalies. The results of our studies indicate that factors in the different genetic backgrounds contribute extensively to the Tcof1 phenotype. Developmental (C) 2004 Wiley-Liss, Inc.