Mammalian Development Section, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Pigment Cell Melanoma Res. 2010 Dec;23(6):729-35. doi: 10.1111/j.1755-148X.2010.00759.x. Epub 2010 Sep 2.
The history of the discovery of the microphthalmia locus and its gene, now called Mitf, is a testament to the triumph of serendipity. Although the first microphthalmia mutation was discovered among the descendants of a mouse that was irradiated for the purpose of mutagenesis, the mutation most likely was not radiation induced but occurred spontaneously in one of the parents of a later breeding. Although Mitf might eventually have been identified by other molecular genetic techniques, it was first cloned from a chance transgene insertion at the microphthalmia locus. And although Mitf was found to encode a member of a well-known transcription factor family, its analysis might still be in its infancy had Mitf not turned out to be of crucial importance for the physiology and pathology of many distinct organs, including eye, ear, immune system, bone, and skin, and in particular for melanoma. In fact, near seven decades of Mitf research have led to many insights about development, function, degeneration, and malignancies of a number of specific cell types, and it is hoped that these insights will one day lead to therapies benefitting those afflicted with diseases originating in these cell types.
小眼畸形基因及其蛋白(现在称为 Mitf)的发现历史充分证明了机缘巧合的胜利。尽管第一个小眼畸形突变是在为诱变目的而辐照的老鼠的后代中发现的,但该突变很可能不是辐射诱导的,而是在后来繁殖的一个父母的某个个体中自发发生的。虽然 Mitf 最终可能会通过其他分子遗传学技术被识别,但它最初是从小眼畸形基因座的一个偶然转基因插入中克隆出来的。尽管 Mitf 被发现编码一个已知转录因子家族的成员,但如果 Mitf 对包括眼睛、耳朵、免疫系统、骨骼和皮肤在内的许多不同器官的生理和病理,特别是黑色素瘤的重要性不大,那么对其分析可能仍处于起步阶段。事实上,近 70 年的 Mitf 研究已经为许多特定细胞类型的发育、功能、退化和恶性肿瘤提供了许多见解,人们希望这些见解有一天能为那些受这些细胞类型起源的疾病影响的人带来治疗益处。