Knockin Animal Models of Inherited Arrhythmogenic Diseases: What Have We Learned From Them?


  • This work was supported by NIH/NHLBI HL58030,d HL66096, and an Established Investigator Award from the American Heart Association 0540048N.

  • Manuscript received 1 April 2007; Revised manuscript received 20 April 2007; Accepted for publication 25 April 2007.

  • Editor: Silva G. Priori, M.D., Ph.D.

Address for correspondence: Barry London, M.D., Ph.D., Cardiovascular Institute, University of Pittsburgh Medical Center, Scaife S-572, 200 Lothrop Street, Pittsburgh, PA 15213. Fax: (412) 647-3913; E-mail:


Mouse models are becoming an increasingly accepted method of studying human diseases. Knockin and knockout techniques have several advantages over traditional transgenic overexpression, and the versatility of the knockin mouse allows the study of both gain of function mutations through targeted mutagenesis, as well as the replacement of one gene by another functional gene. Here, we will review the methods available to generate knockin mice; provide an overview of the techniques used to study electrophysiology in the mice at the cellular, organ, and whole animal level; and highlight knockin mice that have implications for inherited arrhythmias. Specifically, we will focus on models that used knockin mice to clarify gene expression, identify similarities and differences between related genes, and model human arrhythmia syndromes. Our goal is to provide the reader with a general understanding of studies done on knockin mouse models of inherited arrhythmias as well as ideas for future directions.