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Title:
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Short Telomeres, even in the Presence of Telomerase, Limit Tissue Renewal Capacity |
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Author:
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Greider, Carol W.; Huso, David; Feldser, David M.; Karim, Baktiar; Strong, Margaret A.; Armanios, Mary; Hao, Ling-Yang |
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Abstract:
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Autosomal-dominant dyskeratosis congenita is associated with heterozygous mutations in telomerase. To examine the dosage effect of telomerase, we generated a line of mTR+/ÿ mice on the CAST/EiJ background, which has short telomeres. Interbreeding of heterozygotes resulted in progressive telomere shortening, indicating that limiting telomerase compromises telomere mainte- nance. In later-generation heterozygotes, we observed a decrease in tissue renewal capacity in the bone marrow, intestines, and testes that resembled defects seen in dyskeratosis congenita patients. The pro- gressive worsening of disease with decreasing telomere length suggests that short telo- meres, not telomerase level, cause stem cell failure. Further, wild-type mice derived from the late-generation heterozygous parents, termed wt*, also had short telomeres and displayed a germ cell defect, indicating that telomere length determines these phenotypes. We propose that short telomeres in mice that have normal telomerase levels can cause an occult form of genetic disease. |
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URI:
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http://jhir.library.jhu.edu/handle/1774.2/33664
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Date:
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2005-12-16 |
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Citation:
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Reprinted from Cell 123 (6), Hao, Ling-Yang, et al. "Short Telomeres, even in the Presence of Telomerase, Limit Tissue Renewal Capacity" (2005 Dec. 16): 1121-1131 with permission from Elsevier. Original article: http://www.cell.com
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Subject:
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Testis/pathology
Telomerase/genetics
Intestines/pathology
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