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

被引:73
作者
Dixon, J
Dixon, MJ
机构
[1] Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England
[2] Univ Manchester, Dept Dent Med & Surg, Manchester M13 9PT, Lancs, England
关键词
craniofacial defects; phenotypic variation; Treacher Collins syndrome; Tcof1; genetic background;
D O I
10.1002/dvdy.20004
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
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.
引用
收藏
页码:907 / 914
页数:8
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