Conditional ablation of nonmuscle myosin II-B delineates heart defects in adult mice

Xuefei Ma, Kazuyo Takeda, Aman Singh, Zu Xi Yu, Patricia Zerfas, Anthony Blount, Chengyu Liu, Jeffrey Towbin, Michael D. Schneider, Robert S. Adelstein, Qize Wei

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

RATIONALE:: Germline ablation of the cytoskeletal protein nonmuscle myosin II (NMII)-B results in embryonic lethality, with defects in both the brain and heart. Tissue-specific ablation of NMII-B by a Cre recombinase strategy should prevent embryonic lethality and permit study of the function of NMII-B in adult hearts. OBJECTIVE:: We sought to understand the function of NMII-B in adult mouse hearts and to see whether the brain defects found in germline-ablated mice influence cardiac development. METHODS AND RESULTS:: We used a loxP/Cre recombinase strategy to specifically ablate NMII-B in the brains or hearts of mice. Mice ablated for NMII-B in neural tissues die between postnatal day 12 and 22 without showing cardiac defects. Mice deficient in NMII-B only in cardiac myocytes (B/B mice) do not show brain defects. However, B/B mice display novel cardiac defects not seen in NMII-B germline-ablated mice. Most of the B/B mice are born with enlarged cardiac myocytes, some of which are multinucleated, reflecting a defect in cytokinesis. Between 6 to 10 months, they develop a cardiomyopathy that includes interstitial fibrosis and infiltration of the myocardium and pericardium with inflammatory cells. Four of 5 B/B hearts develop marked widening of intercalated discs. CONCLUSIONS:: By avoiding the embryonic lethality found in germline-ablated mice, we were able to study the function of NMII-B in adult mice and show that absence of NMII-B in cardiac myocytes results in cardiomyopathy in the adult heart. We also define a role for NMII-B in maintaining the integrity of intercalated discs.

Original languageEnglish (US)
Pages (from-to)1102-1109
Number of pages8
JournalCirculation research
Volume105
Issue number11
DOIs
StatePublished - Nov 1 2009
Externally publishedYes

Fingerprint

Nonmuscle Myosin Type IIB
Myosin Type II
Cardiac Myocytes
Brain
Cardiomyopathies
Cytoskeletal Proteins
Cytokinesis
Pericardium

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Ma, X., Takeda, K., Singh, A., Yu, Z. X., Zerfas, P., Blount, A., ... Wei, Q. (2009). Conditional ablation of nonmuscle myosin II-B delineates heart defects in adult mice. Circulation research, 105(11), 1102-1109. https://doi.org/10.1161/CIRCRESAHA.109.200303

Conditional ablation of nonmuscle myosin II-B delineates heart defects in adult mice. / Ma, Xuefei; Takeda, Kazuyo; Singh, Aman; Yu, Zu Xi; Zerfas, Patricia; Blount, Anthony; Liu, Chengyu; Towbin, Jeffrey; Schneider, Michael D.; Adelstein, Robert S.; Wei, Qize.

In: Circulation research, Vol. 105, No. 11, 01.11.2009, p. 1102-1109.

Research output: Contribution to journalArticle

Ma, X, Takeda, K, Singh, A, Yu, ZX, Zerfas, P, Blount, A, Liu, C, Towbin, J, Schneider, MD, Adelstein, RS & Wei, Q 2009, 'Conditional ablation of nonmuscle myosin II-B delineates heart defects in adult mice', Circulation research, vol. 105, no. 11, pp. 1102-1109. https://doi.org/10.1161/CIRCRESAHA.109.200303
Ma, Xuefei ; Takeda, Kazuyo ; Singh, Aman ; Yu, Zu Xi ; Zerfas, Patricia ; Blount, Anthony ; Liu, Chengyu ; Towbin, Jeffrey ; Schneider, Michael D. ; Adelstein, Robert S. ; Wei, Qize. / Conditional ablation of nonmuscle myosin II-B delineates heart defects in adult mice. In: Circulation research. 2009 ; Vol. 105, No. 11. pp. 1102-1109.
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AU - Takeda, Kazuyo

AU - Singh, Aman

AU - Yu, Zu Xi

AU - Zerfas, Patricia

AU - Blount, Anthony

AU - Liu, Chengyu

AU - Towbin, Jeffrey

AU - Schneider, Michael D.

AU - Adelstein, Robert S.

AU - Wei, Qize

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N2 - RATIONALE:: Germline ablation of the cytoskeletal protein nonmuscle myosin II (NMII)-B results in embryonic lethality, with defects in both the brain and heart. Tissue-specific ablation of NMII-B by a Cre recombinase strategy should prevent embryonic lethality and permit study of the function of NMII-B in adult hearts. OBJECTIVE:: We sought to understand the function of NMII-B in adult mouse hearts and to see whether the brain defects found in germline-ablated mice influence cardiac development. METHODS AND RESULTS:: We used a loxP/Cre recombinase strategy to specifically ablate NMII-B in the brains or hearts of mice. Mice ablated for NMII-B in neural tissues die between postnatal day 12 and 22 without showing cardiac defects. Mice deficient in NMII-B only in cardiac myocytes (B/B mice) do not show brain defects. However, B/B mice display novel cardiac defects not seen in NMII-B germline-ablated mice. Most of the B/B mice are born with enlarged cardiac myocytes, some of which are multinucleated, reflecting a defect in cytokinesis. Between 6 to 10 months, they develop a cardiomyopathy that includes interstitial fibrosis and infiltration of the myocardium and pericardium with inflammatory cells. Four of 5 B/B hearts develop marked widening of intercalated discs. CONCLUSIONS:: By avoiding the embryonic lethality found in germline-ablated mice, we were able to study the function of NMII-B in adult mice and show that absence of NMII-B in cardiac myocytes results in cardiomyopathy in the adult heart. We also define a role for NMII-B in maintaining the integrity of intercalated discs.

AB - RATIONALE:: Germline ablation of the cytoskeletal protein nonmuscle myosin II (NMII)-B results in embryonic lethality, with defects in both the brain and heart. Tissue-specific ablation of NMII-B by a Cre recombinase strategy should prevent embryonic lethality and permit study of the function of NMII-B in adult hearts. OBJECTIVE:: We sought to understand the function of NMII-B in adult mouse hearts and to see whether the brain defects found in germline-ablated mice influence cardiac development. METHODS AND RESULTS:: We used a loxP/Cre recombinase strategy to specifically ablate NMII-B in the brains or hearts of mice. Mice ablated for NMII-B in neural tissues die between postnatal day 12 and 22 without showing cardiac defects. Mice deficient in NMII-B only in cardiac myocytes (B/B mice) do not show brain defects. However, B/B mice display novel cardiac defects not seen in NMII-B germline-ablated mice. Most of the B/B mice are born with enlarged cardiac myocytes, some of which are multinucleated, reflecting a defect in cytokinesis. Between 6 to 10 months, they develop a cardiomyopathy that includes interstitial fibrosis and infiltration of the myocardium and pericardium with inflammatory cells. Four of 5 B/B hearts develop marked widening of intercalated discs. CONCLUSIONS:: By avoiding the embryonic lethality found in germline-ablated mice, we were able to study the function of NMII-B in adult mice and show that absence of NMII-B in cardiac myocytes results in cardiomyopathy in the adult heart. We also define a role for NMII-B in maintaining the integrity of intercalated discs.

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