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2015年6月3日 讯 /生物谷BIOON/ –理解骨骼发育的复杂性不仅是人类生物学研究的一个重要领域，其对于医学工程领域开发治疗骨骼障碍的新型疗法也至关重要；人类的身高是一种可遗传的典型多基因性状，研究者研究了很多年为阐明人类生长发育提供了许多创新型的观点；研究者发现有很多候选基因都和决定人类机体身高有关，然而目前他们并不清楚这些基因如何直接影响机体身高和骨骼发育。
近日，来自弗吉尼亚联邦大学的研究者就鉴别出了精子中特殊基因和人类身高之间的关联；研究者发现，精子相关的抗原17（SPAG17）基因的靶向突变会导致小鼠骨骼发育畸形，比如后肢长度变短、胸骨出现融合性片段以及骨中矿物质缺失等。Jerome Strauss III博士表示，对小鼠进行研究就告诉我们SPAG17和骨骼长度直接相关，这或许就可以帮助解释为何精子和机体身高直接相关。
相关研究以“Spag17 Deficiency Results in Skeletal Malformations and Bone Abnormalities”为题刊登于国际杂志PLoS ONE上。当研究影响男性不育的基因时，研究者首次发现SPAG17基因，该基因参与了精子的运动型，当进行工程化操作制造缺失SPAG17的小鼠后，研究者就可以在小鼠体内观察到不育的表型，相比野生型小鼠，缺失SPAG17的小鼠往往会在出生后12消失内死亡，而且胫骨和股骨会变短，同时也会表现出骨质畸形和骨矿化缺失的现象。
随后研究者分析了缺失SPAG17的小鼠的骨质形状以及胚胎发育情况，同时在培养基中对离体骨细胞进行培养，目的是为了确定形成骨质的细胞能力是否还会出现任何改变，最后研究者发现，小鼠骨质畸形是由于SPAG17基因的沉默导致，而成骨细胞和软骨细胞则会表达该基因。
目前还需要进行更多的研究来阐明SPAG17在骨质发育和结构形成中的作用；研究者的研究揭示了SPAG17的功能，并且延伸了该基因对于骨骼发育、生长以及矿化调节的重要角色的认知，下一步研究者将通过更为深入的研究来阐明为何SPAG17基因会影响机体骨骼的发育，同时研究者还将进行临床试验在人类机体中进行研究。（基因宝jiyinbao.com）
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Spag17 Deficiency Results in Skeletal Malformations and Bone Abnormalities
Maria Eugenia Teves, Gobalakrishnan Sundaresan, David J. Cohen, Sharon L. Hyzy, Illya Kajan, Melissa Maczis, Zhibing Zhang, Richard M. Costanzo, Jamal Zweit, Zvi Schwartz, Barbara D. Boyan, Jerome F. Strauss III
Height is the result of many growth and development processes. Most of the genes associated with height are known to play a role in skeletal development. Single-nucleotide polymorphisms in the SPAG17 gene have been associated with human height. However, it is not clear how this gene influences linear growth. Here we show that a targeted mutation in Spag17 leads to skeletal malformations. Hind limb length in mutants was significantly shorter than in wild-type mice. Studies revealed differences in maturation of femur and tibia suggesting alterations in limb patterning. Morphometric studies showed increased bone formation evidenced by increased trabecular bone area and the ratio of bone area to total area, leading to reductions in the ratio of marrow area/total area in the femur. Micro-CTs and von Kossa staining demonstrated increased mineral in the femur. Moreover, osteocalcin and osterix were more highly expressed in mutant mice than in wild-type mice femurs. These data suggest that femur bone shortening may be due to premature ossification. On the other hand, tibias appear to be shorter due to a delay in cartilage and bone development. Morphometric studies showed reduction in growth plate and bone formation. These defects did not affect bone mineralization, although the volume of primary bone and levels of osteocalcin and osterix were higher. Other skeletal malformations were observed including fused sternebrae, reduced mineralization in the skull, medial and metacarpal phalanges. Primary cilia from chondrocytes, osteoblasts, and embryonic fibroblasts (MEFs) isolated from knockout mice were shorter and fewer cells had primary cilia in comparison to cells from wild-type mice. In addition, Spag17 knockdown in wild-type MEFs by Spag17 siRNA duplex reproduced the shorter primary cilia phenotype. Our findings disclosed unexpected functions for Spag17 in the regulation of skeletal growth and mineralization, perhaps because of its role in primary cilia of chondrocytes and osteoblasts.