Inhibition of class IIb histone deacetylase significantly improves cloning efficiency in mice.
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.
Ono
Tetsuo
T
Laboratory for Genomic Reprogramming, RIKEN Center for Developmental Biology, Kobe, Japan.
Li
Chong
C
Mizutani
Eiji
E
Terashita
Yukari
Y
Yamagata
Kazuo
K
Wakayama
Teruhiko
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D065150:Cellular Reprogramming / Q000187:drug effects*; D019976:Cloning, Organism / Q000379:methods*; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D053652:Nuclear Transfer Techniques; D009865:Oocytes / Q000187:drug effects; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology; D000077337:Vorinostat
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007527:Isoenzymes; C100692:oxamflatin; D000077337:Vorinostat; D014635:Valproic Acid; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2