Mammalian DNA topoisomerase IIIα is essential in early embryogenesis

Targeted disruption of the mouse TOP3 alpha gene encoding DNA topoisomerase III alpha was carried out to study the physiological functions of the mammalian type IA DNA topoisomerase, Whereas heterozygous top3 alpha(+/-) mutant mice were found to resemble phenotypically their TOP3 alpha(+/+) litermates, no viable top3 alpha(-/-) homozygotes were found among over 100 progeny of top3 alpha(+/-) intercrosses. Examination of embryos dissected from decidual swellings and in vitro culturing of blastocysts from top3 alpha(+/-) intercrosses showed that implantation of top3 alpha(-/-) 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 III alpha 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.