Potassium channel subunit Kcne2 Knockout Mice
- Others
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- (2006) Roepke, T. K., et al. The KCNE2 potassium channel ancillary subunit is essential for gastric acid secretion. J. Biol. Chem. 281,23740-23747
- (2008) Roepke, T.K. et al. Targeted deletion of Kcne2 impairs ventricular repolarization via disruption of I(K,slow1( and I(to,f). FASEB J. 22: 3648-3660
- (2009) Roepke TK et al. Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis. Nat Med 15(10):1186-94.
- *Abstract
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Biological material
Transgenic Kcne2 gene knockout mice
Details: Kcne2 was disrupted in RF8 129/SvJae murine embryonic stem (ES) cells by homologous recombination using standard techniques. Correctly targeted ES cells were aggregated with C57BL/6 mouse blastocysts and implanted into C57BL/6 female mice to generate chimeric progeny. The chimeric progeny were bred to C57BL/6 mice to generate 50:50 129/SvJae:C57BL/6 progeny, which in turn were interbred to generate the colony. (full description in 2006 JBC article linked below)
Uses
- Basic research in the fields of cardiology, gastroenterology, endocrinology, and CNS/PNS
- In vivo models for preclinical drug development
Phenotype
- GI: Severe gastric phenotype with profoundly reduced parietal cell proton secretion, abnormal parietal cell morphology, achlorhydria, hypergastrinemia, and striking gastric glandular hyperplasia
- Cardiac: hypertrophy, fibrosis, and reduced fractional shortening; compromised ventricular repolarization (50% reduction in potassium "slow,1" current generated by Kv1.5; 25% reduction in potassium "to,f" current generated by Kv4 subunits); lengthened QTc under sevoflurane anesthesia
- Endocrine: hypothyroidism, dwarfism, alopecia, goiter
Voltage-gated potassium (Kv) channels are essential for repolarization of excitable cells, including cardiac myocytes. Genes in the KCNE family encode the MinK-related peptides (MiRPs), single-transmembrane domain proteins that coassemble with Kv channel subunits to alter potassium channels' gating, conductance, and pharmacology. The functional effects of MiRPs on different Kv channels are diverse and often profound. Inherited or sporadic mutations in the human KCNE2 gene associate with inherited long QT syndrome, and common KCNE2 polymorphisms increase susceptibility to drug-induced long QT syndrome.
KCNE2 is also expressed in a variety of other tissues, including thyroid, brain, and parietal cells of the stomach.
- *Licensing
- Vibhu Sachdev(212) 746-6187sachdev@cornell.edu
- Country/Region
- USA
