Research perspectives in inherited lymphatic disease
Research perspectives in inherited lymphatic disease
复制标题
DOI：
10.1111/j.1749-6632.2002.tb04866.x
复制
发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Ferrell, RE
中科院分区：
文献类型：
--
作者：
Ferrell, RE
遗传性淋巴水肿提供了一个机会，以确定基因参与正常和紊乱的淋巴发育。对Milroy病家族的遗传分析确定VEGFR 3突变是先天性水肿的原因，证实了VEGFC/VEGFR 3信号传导在淋巴发育中的重要性。这些观察结果导致了原发性脑水肿的小鼠模型的鉴定，并且使用转基因和基因转移技术对该小鼠模型的后续分析为原发性脑水肿的生物学治疗的开发提供了初步线索。从公共卫生的角度来看，更重要的是，操纵这一途径可能会导致更普遍的继发性水肿形式的有效治疗。FOXC 2基因突变的鉴定，在水肿-双歧综合征揭示了新的淋巴发育的分子见解。FOXC 2通路的分子分析可能为淋巴系统共享的发育通路和与这种复杂综合征相关的其他发育异常提供线索。随着人类基因组知识的不断提高，对水肿家族的遗传分析继续为识别影响淋巴发育的基因提供最有前途的方法之一。
The hereditary lymphedemas provide an opportunity to identify genes involved in normal and deranged lymphatic development. Genetic analysis of families with Milroy's disease identified mutations in VEGFR3 as a cause of congenital lymphedema, confirming the importance of VEGFC/VEGFR3 signaling in lymphatic development. These observations led to the identification of a mouse model for primary lymphedema, and subsequent analysis of this mouse model, using transgenic and gene transfer techniques, has provided initial clues to the development of a biologically based therapy for primary lymphedema. Of more importance from a public health perspective is the fact that manipulation of this pathway may lead to effective therapies for the more prevalent forms of secondary lymphedema. Identification of FOXC2 as, the gene mutated in the lymphedema-distichiasis syndrome has revealed new molecular insight into lymphatic development. Molecular analysis of the FOXC2 pathway may provide clues to developmental pathways shared by the lymphatic system and the other developmental abnormalities associated with this complex syndrome. With improving knowledge of the human genome, genetic analysis of families with lymphedema continues to offer one of the most promising approaches to identifying genes influencing lymphatic development.