Mammalian DNA topoisomerase IIIα is essential in early embryogenesis

Targeted disruption of the mouse TOP3α gene encoding DNA topoisomerase IIIα was carried out to study the physiological functions of the mammalian type IA DNA topoisomerase. Whereas heterozygous top3α(+/−) mutant mice were found to resemble phenotypically their TOP3α(+/+) litermates, no viable top3α(−/−) homozygotes were found among over 100 progeny of top3α(+/−) intercrosses. Examination of embryos dissected from decidual swellings and in vitro culturing of blastocysts from top3α(+/−) intercrosses showed that implantation of top3α(−/−) 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 IIIα 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.