Cloned mouse HCN2 and Kv4.2 ion channel promoters

Objective: To isolate and characterize the promoters of the mouse HCN2 and Kv4.2 ion channels

Background: The recently cloned family of HCN (hyperpolarization activated cyclic nucleotide gated) ion channels is critically involved in regulating heart rate. Therefore, it may play an important role in many pathophysiologies with cardiac manifestations, such as hypothyroidism. Kv4.2 has also been implicated in hypothyroidism.

Methods: The mouse HCN2 promoter was isolated by screening a mouse genomic library with a probe internal to the first exon of the mouse HCN2 gene. Fragments up to 5.5 kb were cloned into luciferase or CAT expression vectors and transfected into rat neonatal cardiac myocytes or HEK-293 cells. The response to triiodothyronine (T₃) is currently being evaluated. 3 kB of HCN2 promoter sequence was newly sequenced and submitted to GenBank (AF211837).

The mouse Kv4.2 promoter was isolated from the mouse genomic library and subcloned, and is currently being characterized.

Results: This study is currently in progress. Preliminary results are unpublished.