Division of Pediatric Blood and Marrow Transplantation Program, University of Minnesota, Minneapolis, MN, USA.
PLoS One. 2009 Nov 6;4(11):e7688. doi: 10.1371/journal.pone.0007688.
The zebrafish is an increasingly popular model for studying many aspects of biology. Recently, ztert, the zebrafish homolog of the mammalian telomerase gene has been cloned and sequenced. In contrast to humans, it has been shown that the zebrafish maintains telomerase activity for much of its adult life and has remarkable regenerative capacity. To date, there has been no longitudinal study to assess whether this retention of telomerase activity equates to the retention of chromosome telomere length through adulthood.
METHODOLOGY/PRINCIPAL FINDINGS: We have systematically analyzed individual organs of zebrafish with regard to both telomere length and telomerase activity at various time points in its adult life. Heart, gills, kidney, spleen, liver, and intestine were evaluated at 3 months, 6 months, 9 months, and 2 years of age by Southern blot analysis. We found that telomeres do not appreciably shorten throughout the lifespan of the zebrafish in any organ. In addition, there was little difference in telomere lengths between organs. Even when cells were under the highest pressure to divide after fin-clipping experiments, telomere length was unaffected. All aged (2 year old) tissues examined also expressed active amounts of telomerase activity as assessed by TRAP assay.
CONCLUSIONS/SIGNIFICANCE: In contrast to several other species including humans, the retention of lifelong telomerase and telomeres, as we have reported here, would be necessary in the zebrafish to maintain its tremendous regenerative capacity. The ongoing study of the zebrafish's ability to maintain telomerase activity may be helpful in unraveling the complexity involved in the maintenance (or lack thereof) of telomeres in other species such the mouse or human.
斑马鱼作为研究生物学诸多方面的模型正日益受到欢迎。最近,已克隆并测序了斑马鱼中哺乳动物端粒酶基因的同源基因ztert。与人类不同,研究表明斑马鱼在成年后的大部分时间里都保持端粒酶活性,并且具有显著的再生能力。迄今为止,尚无纵向研究来评估这种端粒酶活性的保留是否等同于成年期染色体端粒长度的保留。
方法/主要发现:我们系统地分析了斑马鱼成年期不同时间点各个器官的端粒长度和端粒酶活性。通过Southern印迹分析,在3个月、6个月、9个月和2岁时对心脏、鳃、肾脏、脾脏、肝脏和肠道进行了评估。我们发现,在斑马鱼的整个生命周期中,任何器官的端粒都没有明显缩短。此外,各器官之间的端粒长度差异很小。即使在剪鳍实验后细胞处于最高分裂压力下,端粒长度也未受影响。通过TRAP分析评估,所有检测的老年(2岁)组织也都表达了活性水平的端粒酶活性。
结论/意义:与包括人类在内的其他几个物种不同,正如我们在此报道的那样,斑马鱼必须保留终身端粒酶和端粒,以维持其巨大的再生能力。对斑马鱼维持端粒酶活性能力的持续研究可能有助于揭示其他物种(如小鼠或人类)端粒维持(或缺乏维持)所涉及的复杂性。