Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Cardiac arrhythmia

Knock-in swine model reveals new arrhythmia mechanism in Timothy syndrome

Nature Cardiovascular Research volume 3, pages 18–20 (2024)Cite this article

Subjects

Timothy syndrome is a severe variant of long QT syndrome, but an accurate in vivo model to study the disease and identify treatments has been lacking. A knock-in swine model of Timothy syndrome now shows that CaMKII-mediated reduction in peak INa slows the cardiac impulse propagation and contributes to the severe arrhythmia in the disorder.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Mechanisms underlying initiation and maintenance of arrhythmias in Timothy syndrome.

References

  1. Bagnall, R. D. et al. N. Engl. J. Med. 374, 2441–2452 (2016).

    Article  PubMed  Google Scholar 

  2. Schwartz, P. J. et al. Circulation 120, 1761–1767 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Krijger Juárez, C. et al. 9, 124–138 (2023).

  4. Wilde, A. A. M. et al. Europace. 24, 1307–1367 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Splawski, I. et al. Cell 119, 19–31 (2004).

    Article  CAS  PubMed  Google Scholar 

  6. Dick, I. E. et al. Nat. Commun. 7, 10370 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Porta-Sánchez, A. et al. Nat. Cardiovasc. Res. https://doi.org/10.1038/s44161-023-00393-w (2023).

    Article  Google Scholar 

  8. Clauss, S. et al. Nat. Rev. Cardiol. 16, 457–475 (2019).

    Article  PubMed  Google Scholar 

  9. Child, N. et al. Heart Rhythm. 12, 1644–1653 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Boukens, B. J. et al. J. Physiol. 592, 4613–4626 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Thiel, W. H. et al. Circulation 25, 2225–2234 (2008).

    Article  Google Scholar 

  12. Aiba, T. et al. Cardiovasc. Res. 85, 454–463 (2010).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

C.R.B. received support from EJP-RD (LQTS-NEXT, ZonMW project 40-46300-98-19009), the Leducq Foundation (project 17CVD02) and the Dutch Heart Foundation (CVON 2018-30 PREDICT2).

Author information

Authors and Affiliations

  1. Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

    Bastiaan J. Boukens

  2. Department of Medical Biology, Amsterdam University Medical Center, Amsterdam, The Netherlands

    Bastiaan J. Boukens & Arie O. Verkerk

  3. Department of Experimental Cardiology, Amsterdam University Medical Center, Amsterdam, The Netherlands

    Arie O. Verkerk & Connie R. Bezzina

Authors
  1. Bastiaan J. Boukens
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arie O. Verkerk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Connie R. Bezzina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Bastiaan J. Boukens or Connie R. Bezzina.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Boukens, B.J., Verkerk, A.O. & Bezzina, C.R. Knock-in swine model reveals new arrhythmia mechanism in Timothy syndrome. Nat Cardiovasc Res 3, 18–20 (2024). https://doi.org/10.1038/s44161-023-00408-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s44161-023-00408-6

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing