Missense mutation in the mouse Col2al gene causes spondyloepiphyseal dysplasia congenita, hearing loss, and retinoschisis
Missense mutation in the mouse Col2al gene causes spondyloepiphyseal dysplasia congenita, hearing loss, and retinoschisis
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DOI：
10.1359/jbmr.2003.18.9.1612
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发表时间：
2003-09-01
影响因子：
6.2
通讯作者：
Davisson, MT
中科院分区：
文献类型：
--
作者：
Donahue, LR;Chang, B;Davisson, MT
简介：发现了一种新的小鼠常染色体隐性遗传突变，命名为先天性脊椎骨骺发育不良（spondyloepiphyseal dysplasia congenita，基因符号sedc）。成年人有缩短的鼻子，发育不良的椎骨，股骨和胫骨，加上视网膜劈裂和听力损失。结果：序列分析表明，该基因为Col 2a 1，其第48外显子发生错义突变，导致第1417位氨基酸由精氨酸变为半胱氨酸。两个人脊椎骨骺发育不良（SED）先天性已被报道与相同的氨基酸取代位置789在人类COL 2A 1 gene.Conclusions：因此，sedc/sedc小鼠提供了一个有价值的模型，人类SED先天性分子和表型同源性。使用sedc/sedc小鼠进行的进一步生化分析、分子建模和细胞培养研究可以深入了解依赖于Col 2a 1的骨骼发育机制及其在原纤维形成和软骨模板组织中的作用。
Introduction: A new mouse autosomal recessive mutation has been discovered and named spondyloepiphyseal dysplasia congenita (gene symbol sedc).Materials and Methods: Homozygous sedc mice can be identified at birth by their small size and shortened trunk. Adults have shortened noses, dysplastic vertebrae, femora, and tibias, plus retinoschisis and hearing loss. The mutation was mapped to Chr15, and Col2a1 was identified as a candidate gene.Results: Sequence analyses revealed that the affected gene is Col2a1, which has a missense mutation at exon 48 causing an amino acid change of arginine to cysteine at position 1417. Two human patients with spondyloepiphyseal dysplasia (SED) congenita have been reported with the same amino acid substitution at position 789 in the human COL2A1 gene.Conclusions: Thus, sedc/sedc mice provide a valuable model of human SED congenita with molecular and phenotypic homology. Further biochemical analyses, molecular modeling, and cell culture studies using sedc/sedc mice could provide insight into mechanisms of skeletal development dependent on Col2a1 and its role in fibril formation and cartilage template organization.