Coviello-McLaughlin G M, Prowse K R
Geron Corporation, 200 Constitution Drive, Menlo Park, CA 94025, USA.
Nucleic Acids Res. 1997 Aug 1;25(15):3051-8. doi: 10.1093/nar/25.15.3051.
Telomere shortening has been causally implicated in replicative senescence in humans. To examine the relationship between telomere length and ageing in mice, we have utilized Mus spretus as a model species because it has telomere lengths of approximately the same length as humans. Telomere length and telomerase were analyzed from liver, kidney, spleen, brain and testis from >180 M.spretus male and female mice of different ages. Although telomere lengths for each tissue were heterogeneous, significant changes in telomere lengths were found in spleen and brain, but not in liver, testis or kidney. Telomerase activity was abundant in liver and testis, but weak to non-detectable in spleen, kidney and brain. Gender differences in mean terminal restriction fragment length were discovered in tissues from M.spretus and from M.spretus xC57BL/6 F1 mice, in which a M. spretus -sized telomeric smear could be measured. The comparison of the rank order of tissue telomere lengths within individual M. spretus showed that certain tissues tended to be longer than the others, and this ranking also extended to tissues of the M.spretus xC57BL/6 F1 mice. These data suggest that telomere lengths within individual tissues are regulated independently and are genetically controlled.
端粒缩短与人类的复制性衰老存在因果关联。为了研究小鼠端粒长度与衰老之间的关系,我们利用家鼠作为模型物种,因为其端粒长度与人类大致相同。对180多只不同年龄的家鼠雌雄小鼠的肝脏、肾脏、脾脏、大脑和睾丸进行了端粒长度和端粒酶分析。尽管每个组织的端粒长度存在异质性,但在脾脏和大脑中发现了端粒长度的显著变化,而在肝脏、睾丸或肾脏中未发现。端粒酶活性在肝脏和睾丸中丰富,但在脾脏、肾脏和大脑中微弱或无法检测到。在家鼠以及家鼠与C57BL/6 F1杂交小鼠的组织中发现了平均末端限制片段长度的性别差异,在这些组织中可以测量到家鼠大小的端粒涂片。对单个家鼠体内组织端粒长度排序的比较表明,某些组织的端粒往往比其他组织长,这种排序也延伸到家鼠与C57BL/6 F1杂交小鼠的组织中。这些数据表明,单个组织内的端粒长度是独立调节的,并且受基因控制。