研究人員發(fā)明了一種關(guān)節(jié)滑液肉瘤小鼠模型,,使科學(xué)家可以更進(jìn)一步了解這種高度惡化性的軟組織惡性腫瘤之起源和發(fā)病原理。
這項(xiàng)研究發(fā)表于4月號的Cancer Cell中,,研究結(jié)果提供關(guān)節(jié)滑液肉瘤發(fā)生及惡化的時間點(diǎn)和環(huán)境之新信息,。這種小鼠模型還可以用于研發(fā)這種致命性疾病的治療策略。
關(guān)節(jié)滑液肉瘤與一種鑲嵌融合蛋白質(zhì)SYT-SSX的表現(xiàn)有關(guān),?;羧A德休斯醫(yī)學(xué)院和猶他大學(xué)醫(yī)學(xué)院人類遺傳學(xué)部門的Mario R. Capecchi 博士,和同事研發(fā)出可以在特定的細(xì)胞中表現(xiàn)人類SYT-SSX的小鼠模型,。
利用這種方法,,研究人員發(fā)現(xiàn),SYT-SSX表現(xiàn)于成肌細(xì)胞中,,足以導(dǎo)致關(guān)節(jié)滑液肉瘤,,而且達(dá)到100%的外顯率。
SYT-SSX基因是由X染色體短臂第11區(qū)及第18染色體長臂第11區(qū),,發(fā)生染色體轉(zhuǎn)移而形成的融合基因,,這種特征基因幾乎存在于所有的關(guān)節(jié)滑液肉瘤中。SYT-SSX過早表現(xiàn),,會干擾正常發(fā)育,,并與胚胎死亡有關(guān),當(dāng)表現(xiàn)于分化的肌肉細(xì)胞中時,,即使尚未形成腫瘤,,也會導(dǎo)致肌肉細(xì)胞損傷和死亡。
利用條件控制的基因技術(shù),,可以讓研究人員控制融合蛋白質(zhì)表現(xiàn)的時間,,以研究當(dāng)?shù)鞍踪|(zhì)于不同的肌肉發(fā)展階段中表現(xiàn),,會發(fā)生什么情況,。
(資料來源 : Bio.com)
原始出處:
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
[email protected]
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.