Lin X, Gan L, Klein W H, Wells D
Department of Biology and Biochemistry, University of Houston, Texas 77204, USA.
Biochem Biophys Res Commun. 1998 Jul 30;248(3):738-43. doi: 10.1006/bbrc.1998.9050.
Hereditary multiple exostoses (EXT) is a genetically heterogeneous, autosomal dominant skeletal disorder. The gene for EXT1 maps to human chromosome 8q24.1 and encodes an evolutionary conserved protein that is a member of a multigene family. The mouse homolog of human EXT1 protein is 99% similar to its human counterpart. Here, we present the expression profiles of the mouse EXT1 gene. EXT1 mRNA is initially expressed at 6.5 days post-coitum (d.p.c.), which coincides with gastrulation of the mouse embryo. Whole mount in situ hybridization with 10.5 to 12.5 d.p.c. mouse embryos showed a high level of expression of EXT1 mRNA in developing limb buds. Epitope tagging experiments revealed the endoplasmic reticulum localization of EXT1 protein. This localization was consistent with a hydrophobic stretch of amino acids present at the N-terminal end of the EXT1 protein. These results provide novel information on the function of EXT1 and the etiology of hereditary multiple exostoses.
遗传性多发性外生骨疣（EXT）是一种具有遗传异质性的常染色体显性骨骼疾病。EXT1基因定位于人类染色体8q24.1，编码一种进化保守的蛋白质，该蛋白质是一个多基因家族的成员。人类EXT1蛋白的小鼠同源物与其人类对应物相似度为99%。在此，我们展示了小鼠EXT1基因的表达谱。EXT1 mRNA最初在交配后6.5天（d.p.c.）表达，这与小鼠胚胎的原肠胚形成时间一致。对10.5至12.5 d.p.c.的小鼠胚胎进行全胚胎原位杂交显示，EXT1 mRNA在发育中的肢芽中高水平表达。表位标记实验揭示了EXT1蛋白在内质网中的定位。这种定位与EXT1蛋白N末端存在的一段疏水性氨基酸序列一致。这些结果为EXT1的功能以及遗传性多发性外生骨疣的病因提供了新的信息。
