研究人员发明了一种关节滑液肉瘤小鼠模型,使科学家可以更进一步了解这种高度恶化性的软组织恶性肿瘤之起源和发病原理。
这项研究发表于4月号的Cancer Cell中,研究结果提供关节滑液肉瘤发生及恶化的时间点和环境之新信息。这种小鼠模型还可以用于研发这种致命性疾病的治疗策略。
关节滑液肉瘤与一种镶嵌融合蛋白质SYT-SSX的表现有关。霍华德休斯医学院和犹他大学医学院人类遗传学部门的Mario R. Capecchi 博士,和同事研发出可以在特定的细胞中表现人类SYT-SSX的小鼠模型。
利用这种方法,研究人员发现,SYT-SSX表现于成肌细胞中,足以导致关节滑液肉瘤,而且达到100%的外显率。
SYT-SSX基因是由X染色体短臂第11区及第18染色体长臂第11区,发生染色体转移而形成的融合基因,这种特征基因几乎存在于所有的关节滑液肉瘤中。SYT-SSX过早表现,会干扰正常发育,并与胚胎死亡有关,当表现于分化的肌肉细胞中时,即使尚未形成肿瘤,也会导致肌肉细胞损伤和死亡。
利用条件控制的基因技术,可以让研究人员控制融合蛋白质表现的时间,以研究当蛋白质于不同的肌肉发展阶段中表现,会发生什么情况。
(资料来源 : Bio.com)
原始出处:
http://www.bio.com/newsfeatures/newsfeatures_research.jhtml?cid=28200006
部分英文原文:
Cancer Cell, Vol 11, 375-388, 10 April 2007
Article
A Conditional Mouse Model of Synovial Sarcoma: Insights into a Myogenic Origin
Malay Haldar,1 Jeffrey D. Hancock,2,3 Cheryl M. Coffin,4 Stephen L. Lessnick,2,3,5 and Mario R. Capecchi1,6,
1 Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
2 The Division of Pediatric Hematology/Oncology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
3 The Center for Children, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
4 Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
5 Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
6 Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Corresponding author
Mario R. Capecchi
mario.capecchi@genetics.utah.edu
Synovial sarcoma is an aggressive soft-tissue malignancy marked by a unique t(X;18) translocation leading to expression of a chimeric SYT-SSX fusion protein. We report here a mouse model of synovial sarcoma based on conditional expression of the human SYT-SSX2. Using this model, we have identified myoblasts as a potential source of synovial sarcoma. Remarkably, within the skeletal muscle lineage, while expression of the oncoprotein in immature myoblasts leads to induction of synovial sarcoma with 100% penetrance, its expression in more differentiated cells induces myopathy without tumor induction. We also show that early widespread expression of the fusion protein disrupts normal embryogenesis, causing lethality.