Pathogenesis of Human Tuberous Sclerosis

人类结节性硬化症是一种常染色体显性遗传性多系统疾病，其临床表现包括智力低下、癫痫发作和肿瘤性病变。尽管自其在医学文献中首次被描述以来，其本质和发病机制一直不清楚，但分子生物学和遗传学的最新进展使人们能够确定这些疾病的一个或多个致病基因，并深入了解其发病机制，特别是肿瘤的发生过程。由于对人类结节性硬化症的分子机制一无所知，TSC2基因突变(EKER)大鼠在阐明TSC2基因在肾癌发生中的作用以及研究肿瘤发生和/或细胞类型特异性癌变的物种差异方面具有巨大的潜力。此外，在Eker大鼠模型中存在遗传背景对肾癌发生的影响，这些数据表明存在抑制肿瘤生长的修饰基因(S)，鉴定这种修饰基因(S)可能有助于了解人类不同的表型。

Human tuberous sclerosis is an autosomal dominant multisystem disorder characterized by phacomatosis with manifestations that include mental retardation, seizures and neoplastic lesions.Although their nature and pathogenesis had been obscure for more than a century since their fist description in the medical literature, recent advancements in molecular biology and genetics has enabled identification of the responsible gene or genes of these diseases and allowed insight into their pathogenesis and especially their neoplastic process.Because nothing is known about the molecular mechanism of human tuberous sclerosis, the Tsc2 gene mutant (Eker) rat has great potential for elucidating the TSC2 gene role in renal carcinogenesis, as well as studying species-specific differences in tumorigenesis and/or cell-type specific carcinogenesis. Moreover, there are effects of genetic background on renal carcinogenesis in the Eker rat model.These data indicate there is a modifier gene(s) that suppresses the growth of tumors.The identification of such a modifier gene(s) might help to understand diverse phenotypes in humans.