Bellavia D, Checquolo S, Campese A F, Felli M P, Gulino A, Screpanti I
Laboratory of Molecular Pathology, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Oncogene. 2008 Sep 1;27(38):5092-8. doi: 10.1038/onc.2008.230.
The Notch3 gene was identified, at the beginning of 90s, as the third mammalian Notch and was initially reported as being expressed in proliferating neuroepithelium. Since then, increasing evidence has demonstrated a number of structural and functional differences between Notch3 and both Notch1 and Notch2, which exhibit the highest structural similarity among the four mammalian Notch receptors. Possibly due to its more restricted tissue distribution, targeted deletion of murine Notch3 does not lead to embryonic lethality as is observed with targeted deletion of Notch1 and Notch2. However, genetic mutation, amplification and deregulated expression of Notch3 have been correlated with the disruption of cell differentiation in transgenic mice and to development of diseases in mice and humans. This review discusses the possible relationships between the structural differences and the nonredundant roles that Notch3 plays in the pathogenesis of the human disease cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy and in the regulation of murine T-cell differentiation and leukemogenesis.
Notch3基因在20世纪90年代初被鉴定为第三个哺乳动物Notch基因，最初报道其在增殖的神经上皮中表达。从那时起，越来越多的证据表明Notch3与Notch1和Notch2之间存在许多结构和功能差异，Notch1和Notch2在四种哺乳动物Notch受体中结构相似性最高。可能由于其组织分布更受限，与Notch1和Notch2的靶向缺失不同，小鼠Notch3的靶向缺失不会导致胚胎致死。然而，Notch3的基因突变、扩增和表达失调与转基因小鼠细胞分化的破坏以及小鼠和人类疾病的发生有关。本综述讨论了Notch3在人类疾病常染色体显性遗传性脑动脉病伴皮质下梗死和白质脑病发病机制中所起的非冗余作用，以及在小鼠T细胞分化和白血病发生调控中结构差异与这些作用之间的可能关系。
