Mice lacking DNA topoisomerase IIIβ develop to maturity but show a reduced mean lifespan

被引：94

作者：

Kwan, KY ^{[1
]}

Wang, JC ^{[1
]}

机构：

[1] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2001年 / 98卷 / 10期

关键词：

D O I：

10.1073/pnas.101132498

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Targeted gene disruption in the murine TOP3 beta gene-encoding DNA topoisomerase III beta was carried out. In contrast to the embryonic lethality of mutant mice lacking DNA topoisomerase III alpha, top3 beta (-/-)nulls are viable and grow to maturity with no apparent defects. Mice lacking DNA topoisomerase III beta have a shorter life expectancy than their wild-type littermates, however. The mean lifespan of the top3 beta (-/-) mice is about 15 months, whereas that of their wild-type littermates is longer than 2 years. Mortality of the top3 beta (-/-) nulls appears to correlate with lesions in multiple organs, including hypertrophy of the spleen and submandibular lymph nodes, glomerulonephritis, and perivascular infiltrates in various organs. Because the DNA topoisomerase III isozymes are likely to interact with helicases of the RecQ family, enzymes that include the determinants of human Bloom, Werner, and Rothmund-Thomson syndromes, the shortened lifespan of top3 beta (-/-) mice points to the possibility that the DNA topoisomerase III isozymes might be involved in the pathogenesis of progeroid syndromes caused by defective RecQ helicases.

引用

页码：5717 / 5721

页数：5

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