LIMB ALTERATIONS IN BRACHYPODISM MICE DUE TO MUTATIONS IN A NEW MEMBER OF THE TGF-BETA-SUPERFAMILY
LIMB ALTERATIONS IN BRACHYPODISM MICE DUE TO MUTATIONS IN A NEW MEMBER OF THE TGF-BETA-SUPERFAMILY
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DOI：
10.1038/368639a0
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发表时间：
1994-04-14
期刊：
影响因子：
64.8
通讯作者：
LEE, SJ
中科院分区：
文献类型：
--
作者：
STORM, EE;HUYNH, TV;LEE, SJ
突变brachypodism（bp）改变了小鼠四肢骨骼的长度和数量，但保留了中轴骨1，2。它说明了特定基因在控制四足动物肢中个体骨骼元素的形态发生中的重要性3，4。我们现在报告分离了转化生长因子-β（TGF-β）超家族5的三个新成员（生长/分化因子（GDF）5、6和7），并通过绘图、表达模式和测序表明Gdf 5突变是造成BP小鼠骨骼改变的原因。GDF 5和密切相关的GDF 6和GDF 7定义了一个新的与已知的骨和软骨诱导分子相关的因子亚组，骨形态发生蛋白（BMP）6。 对短耳小鼠Bmp 5突变的研究表明，正常骨骼发育也需要至少一种其他BMP基因7。在bp和短耳小鼠中的高度特异性骨骼改变表明BMP家族的不同成员控制哺乳动物骨骼中不同形态特征的形成。
THE mutation brachypodism (bp) alters the length and number of bones in the limbs of mice but spares the axial skeleton1,2. It illustrates the importance of specific genes in controlling the morphogenesis of individual skeletal elements in the tetrapod limb3,4. We now report the isolation of three new members of the transforming growth factor-beta (TGF-beta) superfamily5 (growth/differentiation factors (GDF) 5, 6 and 7) and show by mapping, expression patterns and sequencing that mutations in Gdf5 are responsible for skeletal alterations in bp mice. GDF5 and the closely related GDF6 and GDF7 define a new subgroup of factors related to known bone- and cartilage-inducing molecules, the bone morphogenetic proteins (BMPs)6. Studies of Bmp5 mutations in short ear mice have shown that at least one other BMP gene is also required for normal skeletal development7. The highly specific skeletal alterations in bp and short ear mice suggest that different members of the BMP family control the formation of different morphological features in the mammalian skeleton.