Li W, Wang J C
Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1010-3. doi: 10.1073/pnas.95.3.1010.
Targeted disruption of the mouse TOP3alpha gene encoding DNA topoisomerase IIIalpha was carried out to study the physiological functions of the mammalian type IA DNA topoisomerase. Whereas heterozygous top3alpha+/- mutant mice were found to resemble phenotypically their TOP3alpha+/+ litermates, no viable top3alpha-/- homozygotes were found among over 100 progeny of top3alpha+/- intercrosses. Examination of embryos dissected from decidual swellings and in vitro culturing of blastocysts from top3alpha+/- intercrosses showed that implantation of top3alpha-/- embryos and the induction of decidualization could occur, but viability of these embryos was severely compromised at an early stage of development. The requirement of mouse DNA topoisomerase IIIalpha during early embryogenesis is discussed in terms of its plausible role in chromosome replication and its interaction with the RecQ/SGS1 family of DNA helicases, whose members include the Bloom's syndrome and the Werner's syndrome gene products.
为研究哺乳动物IA型DNA拓扑异构酶的生理功能，对编码DNA拓扑异构酶IIIα的小鼠TOP3α基因进行了靶向破坏。虽然发现杂合子top3α+/-突变小鼠在表型上与其TOP3α+/+同窝小鼠相似，但在top3α+/-杂交的100多个后代中未发现存活的top3α-/-纯合子。对从蜕膜肿胀中取出的胚胎进行检查以及对top3α+/-杂交产生的囊胚进行体外培养，结果表明top3α-/-胚胎能够着床并诱导蜕膜化，但这些胚胎在发育早期的活力严重受损。从小鼠DNA拓扑异构酶IIIα在染色体复制中的可能作用及其与RecQ/SGS1家族DNA解旋酶的相互作用方面，讨论了其在早期胚胎发生过程中的需求，该家族成员包括布卢姆综合征和沃纳综合征的基因产物。
