Venkatesan R N, Price C
Department of Chemistry and Department of Biochemistry, N146 Beadle, University of Nebraska, Lincoln, NE 68588, USA.
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14763-8. doi: 10.1073/pnas.95.25.14763.
Although human and rodent telomeres have been studied extensively, very little is known about telomere dynamics in other vertebrates. Moreover, our current dependence on mice as a model for human tumorigenesis and aging poses a problem because human and mouse telomere biology is very different. To explore whether chickens might provide a more useful model, we have examined telomerase activity and telomere length in chicken tissues as well as in primary cell cultures. Although chicken telomeres resemble human telomeres in that they are 8-20 kb in length, the distribution of telomerase activity in chickens resembles what is found in mice. Active enzyme is present in germline tissue as well as in a wide range of somatic tissues. Because chicken cells exhibit extremely low rates of spontaneous immortalization, this finding indicates that constitutive telomerase expression does not necessarily lead to an increased immortalization frequency. Finally, we found that telomerase activity is greatly down-regulated when primary cultures are established from chicken embryos. Although this down-regulation explains the telomere loss and replicative senescence that we observed in fibroblast cultures, it raises questions concerning how relevant studies of senescence in primary cell cultures are to aging in whole animals.
尽管人类和啮齿动物的端粒已得到广泛研究，但对于其他脊椎动物的端粒动态却知之甚少。此外，我们目前依赖小鼠作为人类肿瘤发生和衰老的模型存在一个问题，因为人类和小鼠的端粒生物学差异很大。为了探究鸡是否可能提供一个更有用的模型，我们检测了鸡组织以及原代细胞培养物中的端粒酶活性和端粒长度。虽然鸡的端粒与人类端粒相似，长度为8 - 20 kb，但鸡中端粒酶活性的分布类似于在小鼠中发现的情况。活性酶存在于生殖系组织以及多种体细胞组织中。由于鸡细胞表现出极低的自发永生化率，这一发现表明组成型端粒酶表达不一定会导致永生化频率增加。最后，我们发现从鸡胚胎建立原代培养物时，端粒酶活性会大幅下调。尽管这种下调解释了我们在成纤维细胞培养物中观察到的端粒丢失和复制性衰老，但它也引发了关于原代细胞培养物中的衰老研究与整个动物衰老的相关性的问题。
