Inhibition of Class IIb Histone Deacetylase Significantly Improves Cloning Efficiency in Mice1

Since the first mouse clone was produced by somatic cell nuclear transfer, the success rate of cloning in mice has been extremely low. Some histone deacetylase inhibitors, such as trichostatin A and scriptaid, have improved the full-term development of mouse clones significantly, but the mechanisms...

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Bibliographic Details
Published inBiology of reproduction Vol. 83; no. 6; pp. 929 - 937
Main Authors Ono, Tetsuo, Li, Chong, Mizutani, Eiji, Terashita, Yukari, Yamagata, Kazuo, Wakayama, Teruhiko
Format Journal Article
LanguageEnglish
Published Society for the Study of Reproduction, Inc 01.12.2010
Subjects
clone
developmental biology
early development
embryo
HDACi
ntES cell
nuclear transfer
reprogramming
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Summary:Since the first mouse clone was produced by somatic cell nuclear transfer, the success rate of cloning in mice has been extremely low. Some histone deacetylase inhibitors, such as trichostatin A and scriptaid, have improved the full-term development of mouse clones significantly, but the mechanisms allowing for this are unclear. Here, we found that two other specific inhibitors, suberoylanilide hydroxamic acid and oxamflatin, could also reduce the rate of apoptosis in blastocysts, improve the full-term development of cloned mice, and increase establishment of nuclear transfer-generated embryonic stem cell lines significantly without leading to obvious abnormalities. However, another inhibitor, valproic acid, could not improve cloning efficiency. Suberoylanilide hydroxamic acid, oxamflatin, trichostatin A, and scriptaid are inhibitors for classes I and IIa/b histone deacetylase, whereas valproic acid is an inhibitor for classes I and IIa, suggesting that inhibiting class IIb histone deacetylase is an important step for reprogramming mouse cloning efficiency.
ISSN:0006-3363
1529-7268
DOI:10.1095/biolreprod.110.085282