Embryonic lethality in mice lacking mismatch-specific thymine DNA glycosylase is partially prevented by DOPS, a precursor of noradrenaline.

Yusuke Saito, Tetsuya Ono, Naoki Takeda, Takehiko Nohmi, Masayuki Seki, Takemi Enomoto, Tetsuo Noda, Yoshihiko Uehara

研究成果: Article査読

8 被引用数 (Scopus)

抄録

Thymine DNA glycosylase (TDG) is involved in the repair of G:T and G:U mismatches caused by hydrolytic deamination of 5-methylcytosine and cytosine, respectively. Recent studies have shown that TDG not only has G-T/U glycosylase activities but also acts in the maintaining proper epigenetic status. In order to investigate the function of TDG in vivo, mice lacking Tdg, Tdg (-/-), were generated. Tdg mutant mice died in utero by 11.5 days post coitum (dpc), although there were no significant differences in the spontaneous mutant frequencies between wild type and Tdg (-/-) embryos. On the other hand, the levels of noradrenaline in 10.5 dpc whole embryos, which is necessary for normal embryogenesis, were dramatically reduced in Tdg (-/-) embryos. Consequently, we tested the effect of D, L-threo-3, 4-dihydroxyphenylserine (DOPS), a synthetic precursor of noradrenaline, on the survival of the Tdg (-/-) embryos. DOPS was given to pregnant Tdg (+/-) mice from 6.5 dpc through drinking water. Most of the Tdg (-/-) embryos were alive at 11.5 dpc, and they were partially rescued up to 14.5 dpc by the administration of DOPS. In contrast, the administration of L-3, 4-dihydroxyphenylalanine (L-DOPA) had marginal effects on Tdg (-/-) embryonic lethality. No embryo was alive without DOPS beyond 11.5 dpc, suggesting that the lethality in (-/-) embryos is partially due to the reduction of noradrenaline. These results suggest that embryonic lethality in Tdg (-/-) embryos is due, in part, to the reduction of noradrenaline levels.

本文言語English
ページ(範囲)75-83
ページ数9
ジャーナルthe tohoku journal of experimental medicine
226
1
DOI
出版ステータスPublished - 2012

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)

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