Wareham K A, Lyon M F, Glenister P H, Williams E D
Nature. 1987;327(6124):725-7. doi: 10.1038/327725a0.
We have investigated age-related reactivation of the X chromosome by devising a model in which reactivation of a single gene in one cell among many can be identified. We have used mice with an X-autosomal translocation giving consistent non-random inactivation of the normal X (as judged by biochemical and cytogenetic techniques), that also carry a defective form of a histochemically demonstrable X-linked enzyme. When the gene for the normal enzyme was located on the inactivated normal X a uniformly negative histochemical picture would be predicted in doubly heterozygous animals. A very small proportion of enzyme-positive cells was found in young animals. This proportion increased very significantly with age, but the patch size did not change, showing that the result was not due to preferential division of enzyme-positive cells, but was instead due to the conversion of previously enzyme-negative to enzyme-positive cells. These observations provide the first evidence with a true X-linked gene for an age-related decrease in the stability of the X-inactivation mechanism.
我们通过设计一种模型来研究X染色体与年龄相关的重新激活，在该模型中，可以识别众多细胞中单个细胞内单个基因的重新激活。我们使用了具有X-常染色体易位的小鼠，这种易位导致正常X染色体持续发生非随机失活（通过生化和细胞遗传学技术判断），这些小鼠还携带一种组织化学可显示的X连锁酶的缺陷形式。当正常酶的基因位于失活的正常X染色体上时，预计双杂合动物的组织化学图像将一致呈阴性。在幼龄动物中发现了极少数酶阳性细胞。这一比例随年龄增长显著增加，但斑块大小没有变化，表明结果不是由于酶阳性细胞的优先分裂，而是由于先前酶阴性细胞转变为酶阳性细胞。这些观察结果首次为一个真正的X连锁基因提供了证据，证明X染色体失活机制的稳定性与年龄相关的下降。
