Hathcock Karen S, Hemann Michael T, Opperman Kay Keyer, Strong Margaret A, Greider Carol W, Hodes Richard J
Experimental Immunology Branch, National Cancer Institute, and National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3591-6. doi: 10.1073/pnas.012549799.
Telomeres are usually maintained about an equilibrium length, and the set point for this equilibrium differs between species and between strains of a given species. To examine the requirement for telomerase in mediating establishment of a new telomere length equilibrium, we generated interspecies crosses with telomerase mTR knockout mice. In crosses between C57BL/6J (B6) and either of two unrelated mouse species, CAST/Ei and SPRET/Ei, telomerase mediated establishment of a new telomere length equilibrium in wild-type mTR(+/+) mice. This new equilibrium was characterized by elongation of the short telomeres of CAST/Ei or SPRET/Ei origin. In contrast, mTR(-/-) offspring of interspecies crosses failed to elongate telomeres. Unexpectedly, haploinsufficiency was observed in mTR(+/-) heterozygous interspecies mice, which had an impaired ability to elongate short SPRET/Ei or CAST/Ei telomeres to the new equilibrium set point that was achieved in wild-type mTR(+/+) mice. These results demonstrate that elongation of telomeres to a new telomere set point requires telomerase and indicate that telomerase RNA may be limiting in vivo.
端粒通常维持在一个平衡长度，并且这个平衡的设定点在不同物种以及同一物种的不同品系之间存在差异。为了研究端粒酶在介导建立新的端粒长度平衡中的作用，我们用端粒酶mTR基因敲除小鼠进行了种间杂交实验。在C57BL/6J（B6）与两种不相关的小鼠物种CAST/Ei和SPRET/Ei中的任一种进行杂交时，端粒酶介导野生型mTR(+/+)小鼠建立了新的端粒长度平衡。这种新的平衡表现为起源于CAST/Ei或SPRET/Ei的短端粒发生延长。相比之下，种间杂交的mTR(-/-)后代未能延长端粒。出乎意料的是，在mTR(+/-)杂合种间小鼠中观察到了单倍剂量不足，它们将短的SPRET/Ei或CAST/Ei端粒延长至野生型mTR(+/+)小鼠所达到的新平衡设定点的能力受损。这些结果表明，将端粒延长至新的端粒设定点需要端粒酶，并表明端粒酶RNA在体内可能是有限的。
