Stable Cell Lines Expressing hERG1a and 1b

TECH FIELD(S)
Drug Discovery - Pre-clinical testing
Research Tools - Cell lines

FEATURES
Cardiac I_Kr channels are targets associated with inherited and acquired long QT syndrome (LQTS), a disorder that can lead to ventricular arrhythmias. Previously, I_Kr channels were thought to be composed solely of subunits encoded by the ‘1a’ transcript of the human ether-a-go-go-related gene, or hERG. Since drugs designed for other therapeutic targets may unintentionally block I_Kr channel activity and cause acquired LQTS, commercially available systems that stably express hERG1a have been used to screen all drugs in development. However, recent studies have shown that I_Kr channels include subunits encoded by both hERG1a and 1b, which are alternative transcripts of the hERG gene. Together these subunits produce the biophysical and pharmacological properties characteristic of the native cardiac I_Kr channel. This technology now provides a line of cultured mammalian cells that express both the hERG1a and 1b subunits. In addition, this invention provides the only known antibody specific for the hERG1b isoform (which cross-reacts with ERG1b of rat and canine as well), and a line of cultured mammalian cells that express hERG1b but not hERG1a.

BENEFITS

• Useful for testing lead compounds and drugs for their potential to block activity of the hERG-1-encoded cardiac I_Kr channel
• More closely mimics the I_Kr channel behavior and subunit composition of cardiac myocytes than do commercially available cell lines
• Useful to screen LQTS patients for mutations in the hERG1b-specific exon
• Allows characterization of phenotypes associated with hERG1a mutations in the context of a cardiac ion channel that more closely resembles I_Kr
• The anti-ERG1b antibody recognizes hERG1b from both humans and non-human animals
• Anti-ERG1b antibody can be used to localize the ERG1b isoform in vivo, probe Western blots for ERG1b, and immunoprecipitate ERG1b protein from cell lysates

INVENTOR(S)
Gail A. Robertson, Eugenia M. Jones, Jinling Wang

INTELLECTUAL PROPERTY STATUS
View U.S. Patent No. 7,510,874 in PDF format

CONTACT INFORMATION
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