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<p>Calcium is fundamental to biological processes, and the calcium-sensing receptor (CaSR) is pivotal for maintaining calcium homeostasis. Dysregulation of CaSR is implicated in cardiovascular diseases and cancers. However, its specific function in cardiac development remains incompletely characterized. To address this, we generated <i>casr</i> knockout zebrafish, analyzed cardiac physiology, and performed transcriptomics to elucidate its mechanism. We established three independent <i>casr</i> knockout lines on a Tuebingen (TU) background. Homozygous mutants exhibited reduced heart size, decreased heart rate, impaired myocardial contractility, diminished cardiac output, spinal curvature, and swim bladder inflation failure. Lethality began at 11 days post-fertilization (dpf). Transcriptomics revealed that <i>casr</i> loss disrupted the cardiac muscle contraction pathway, which was associated with swim bladder defects and mortality. Crucially, in a Tupfel long-fin (TL) background, <i>casr</i><sup>−/−</sup> mutants displayed normal swim bladder development, restored expression of cardiac contraction genes, and significantly improved survival. Our results demonstrate that <i>casr</i> is essential for cardiac function and swim bladder inflation in zebrafish, acting through the Wnt signaling and cardiac muscle contraction pathways. Furthermore, the TL genetic background rescues these developmental defects, highlighting a strong effect of genetic background on phenotypic outcomes.</p>

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Zebrafish casr modulates cardiac structure and function

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月12日

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  • Ling Liu,
  • Yuyao Hu,
  • Binling Xie,
  • Ting Zeng,
  • Guifang Tao,
  • Hao Xie,
  • Qingying Shi,
  • Jinrui Lv,
  • Huaping Xie

摘要

Calcium is fundamental to biological processes, and the calcium-sensing receptor (CaSR) is pivotal for maintaining calcium homeostasis. Dysregulation of CaSR is implicated in cardiovascular diseases and cancers. However, its specific function in cardiac development remains incompletely characterized. To address this, we generated casr knockout zebrafish, analyzed cardiac physiology, and performed transcriptomics to elucidate its mechanism. We established three independent casr knockout lines on a Tuebingen (TU) background. Homozygous mutants exhibited reduced heart size, decreased heart rate, impaired myocardial contractility, diminished cardiac output, spinal curvature, and swim bladder inflation failure. Lethality began at 11 days post-fertilization (dpf). Transcriptomics revealed that casr loss disrupted the cardiac muscle contraction pathway, which was associated with swim bladder defects and mortality. Crucially, in a Tupfel long-fin (TL) background, casr−/− mutants displayed normal swim bladder development, restored expression of cardiac contraction genes, and significantly improved survival. Our results demonstrate that casr is essential for cardiac function and swim bladder inflation in zebrafish, acting through the Wnt signaling and cardiac muscle contraction pathways. Furthermore, the TL genetic background rescues these developmental defects, highlighting a strong effect of genetic background on phenotypic outcomes.