Mice lacking DNA topoisomerase IIIbeta develop to maturity but show a reduced mean lifespan.
Targeted gene disruption in the murine TOP3beta gene-encoding DNA topoisomerase IIIbeta was carried out. In contrast to the embryonic lethality of mutant mice lacking DNA topoisomerase IIIalpha, top3beta(-/-) nulls are viable and grow to maturity with no apparent defects. Mice lacking DNA topoisomerase IIIbeta have a shorter life expectancy than their wild-type littermates, however. The mean lifespan of the top3beta(-/-) mice is about 15 months, whereas that of their wild-type littermates is longer than 2 years. Mortality of the top3beta(-/-) 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 top3beta(-/-) 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.
Kwan
K Y
KY
Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
Wang
J C
JC
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000502:physiology*; D008136:Longevity / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout
D017931:DNA Primers; D004264:DNA Topoisomerases, Type I