Targeted disruption of the cardiac troponin T gene causes sarcomere disassembly and defects in heartbeat within the early mouse embryo

Kiyomasa Nishii, Sachio Morimoto, Reiko Minakami, Yumi Miyano, Kanako Hashizume, Mika Ohta, Dong Yun Zhan, Qun Wei Lu, Yosaburo Shibata

研究成果: Contribution to journalArticle

53 引用 (Scopus)

抜粋

Cardiac troponin T (cTnT) is a component of the troponin (Tn) complex in cardiac myocytes, and plays a regulatory role in cardiac muscle contraction by anchoring two other Tn components, troponin I (TnI) and troponin C, to tropomyosin (Tm) on the thin filaments. In order to determine the in vivo function of cTnT, we created a null cTnT allele in the mouse TNNT2 locus. In cTnT-deficient (cTnT-/-) cardiac myocytes, the thick and thin filaments and α-actinin-positive Z-disk-like structures were not assembled into sarcomere, causing early embryonic lethality due to a lack of heartbeats. TnI was dissociated from Tm in the thin filaments without cTnT. In spite of loss of Tn on the thin filaments, the cTnT-/- cardiac myocytes showed regular Ca2+-transients. These findings indicate that cTnT plays a critical role in sarcomere assembly during myofibrillogenesis in the embryonic heart, and also indicate that the membrane excitation and intracellular Ca2+ handling systems develop independently of the contractile system. In contrast, heterozygous cTnT+/- mice had a normal life span with no structural and functional abnormalities in their hearts, suggesting that haploinsufficiency could not be a potential cause of cardiomyopathies, known to be associated with a variety of mutations in the TNNT2 locus.

元の言語英語
ページ(範囲)65-73
ページ数9
ジャーナルDevelopmental Biology
322
発行部数1
DOI
出版物ステータス出版済み - 10 1 2008

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

フィンガープリント Targeted disruption of the cardiac troponin T gene causes sarcomere disassembly and defects in heartbeat within the early mouse embryo' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用

    Nishii, K., Morimoto, S., Minakami, R., Miyano, Y., Hashizume, K., Ohta, M., Zhan, D. Y., Lu, Q. W., & Shibata, Y. (2008). Targeted disruption of the cardiac troponin T gene causes sarcomere disassembly and defects in heartbeat within the early mouse embryo. Developmental Biology, 322(1), 65-73. https://doi.org/10.1016/j.ydbio.2008.07.007