EXT genes are differentially expressed in bone and cartilage during mouse embryogenesis
EXT genes are differentially expressed in bone and cartilage during mouse embryogenesis
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DOI：
10.1002/1097-0177(200007)218:3
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发表时间：
2000-07
影响因子：
2.5
通讯作者：
D. Stickens;Doris Brown;G. Evans
中科院分区：
文献类型：
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作者：
D. Stickens;Doris Brown;G. Evans
遗传性多发性外生骨疣（HME）是一种遗传异质性疾病，其特征是所有长骨末端的骨突起发育。遗传分析显示HME是一种多基因疾病，与染色体8 q24（EXT 1），11 p11 - 13（EXT 2）和19 p（EXT 3）上的三个基因座相关。EXT 1和EXT 2基因已被克隆并被定义为参与硫酸乙酰肝素合成的糖基转移酶。EST数据库分析表明，其他基因家族成员，EXT样基因（EXTL 1，EXTL 2和EXTL 3），与HME基因座无关。小鼠的EXT 1和EXT 2同源物也已被克隆，并显示分别与它们的人类对应物具有99%和95%的相同性。在这里，我们报告了小鼠EXTL 1基因的鉴定，并显示它与人类EXTL 1基因有74%的相同性。在胚胎发育的各个阶段对所有三种小鼠EXT基因进行了表达研究，在发育中的肢芽中进行了整体原位杂交，结果显示所有三种EXT基因的表达水平都很高。然而，切片胚胎原位杂交显示显着差异的EXT 1，EXT 2和EXTL 1的表达谱。EXT 1和EXT 2基因的相同表达模式支持了最近的观察结果，即两种蛋白质形成糖基转移酶复合物。我们提出了一种外生骨疣形成的模型，该模型基于EXT 1和EXT 2参与印度刺猬/甲状旁腺激素相关肽（PTHrP）信号通路，这是软骨细胞成熟过程的重要调节因子。Dev Dyn 2000;218：452-464.© 2000 Wiley利斯公司
Hereditary multiple exostoses (HME) is a genetically heterogeneous disease characterized by the development of bony protuberances at the ends of all long bones. Genetic analyses have revealed HME to be a multigenic disorder linked to three loci on chromosomes 8q24 (EXT1), 11p11‐13 (EXT2), and 19p (EXT3). The EXT1 and EXT2 genes have been cloned and defined as glycosyltransferases involved in the synthesis of heparan sulfate. EST database analysis has demonstrated additional gene family members, EXT‐like genes (EXTL1, EXTL2, and EXTL3), not associated with a HME locus. The mouse homologs of EXT1 and EXT2 have also been cloned and shown to be 99% and 95% identical to their human counterparts, respectively. Here, we report the identification of the mouse EXTL1 gene and show it is 74% identical to the human EXTL1 gene. Expression studies of all three mouse EXT genes throughout various stages of embryonic development were carried out and whole‐mount in situ hybridization in the developing limb buds showed high levels of expression of all three EXT genes. However, in situ hybridization of sectioned embryos revealed remarkable differences in expression profiles of EXT1, EXT2, and EXTL1. The identical expression patterns found for the EXT1 and EXT2 genes support the recent observation that both proteins form a glycosyltransferase complex. We suggest a model for exostoses formation based on the involvement of EXT1 and EXT2 in the Indian hedgehog/parathyroid hormone‐related peptide (PTHrP) signaling pathway, an important regulator of the chondrocyte maturation process. Dev Dyn 2000;218:452–464. © 2000 Wiley‐Liss, Inc.