山梨医科学雑誌　第23巻4号　97-107(2008)

＜Original＞
Effects of Sirtinol on Early Development of the Cloned Murine Embryos

Shuji HIRATA1), Hiroko FUKASAWA1), Hikaru TAGAYA1), Tomoko SHODA1),
Teruhiko WAKAYAMA2) and Kazuhiko HOSHI3)

Abstract: Since 1996, when Dolly was born, cloned vertebrates have been produced in many species. However, the success rate of animal cloning has remained very low especially in mice. This low rate is a severe hindrance in the application of animal cloning on various fields of studies. Recently, the treatment of reconstructed embryos with trichostatin A (TSA), one of the inhibitors for classes I and II histone deacetylases (HDACs), has been reported to significantly improve the development of cloned mice. In the present study, we have investigated the effect of sirtinol, an inhibitor for class III HDAC, on the early development of a cloned murine embryos. The embryos, reconstructed with an enucleated oocyte and cumulus cell nucleus, were treated with sirtinol during activation and/or for 12 hr after activation. The rate of blastocyst formation was significantly improved by treatment with 100 μM sirtinol for 12 hr after activation. Moreover, six live offspring were born after transfer of the cloned embryos, which were treated with TSA and sirtinol, into surrogate mothers. These resultsindicate that sirtinol improves the early development of cloned murine embryos without adverse effects on subsequent development.

Key words: SCNT (somatic cell nuclear transfer), cloned mouse, early development, HDACi (histone deacetylase inhibitor), sirtinol




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