Small-Conductance Ca2+-Activated Potassium Channel 3 (SK3) transgenic mice
OHSU # 0515
In excitable cells, small-conductance Ca2+-activated potassium channels (SK channels) are responsible for the slow after-hyperpolarization that often follows an action potential. Three SK channel subunits have been molecularly characterized. These channels are found in many types of neurons as well as in some other cell types.
In this invention, the SK3 gene was targeted by homologous recombination for the insertion of a gene switch that permits experimental regulation of SK3 expression while retaining normal SK3 promoter function. SK3 transgenic mice were thus developed. These mice have approximately threefold basal overexpression of SK3, and SK3 expression can be effectively eliminated if desired.
Phylogenetically older brain regions such as the thalamus, basal ganglia, cerebellum, and brainstem show high levels of SK3 gene expression. SK3 channels represent potential therapeutic targets for many disorders.
Some examples of disorders in which SK3 channels play a role include:
· sleep apnea or sudden infant death syndrome
· dopamine related disorders (Parkinson's disease, etc.)
· bipolar disorder
· memory loss associated with aging
· breast cancer cell migration
· urinary bladder infections
· anorexia nervosa
· high blood pressure
SK3 channels also are potentially involved with regulating uterine contractions during labor. Furthermore, SK3 is the only known SK subunit expressed in skeletal muscle where expression is highly induced by denervation and in primary cultured myotubes.
John Adelman received his Ph.D. in Microbiology from Oregon Health & Science University in 1988. He holds a B.S. and an M.S. in Microbiology from the University of Connecticut. After a year as a research assistant at Yale University, he spent five years as a research associate at Genentech. He arrived at the Vollum Institute in 1985, where he did his graduate research. After receiving his Ph.D., he accepted a faculty position at the Vollum and was promoted to senior scientist in 1998. Adelman holds concurrent appointments in the Departments of Cell and Developmental Biology and Molecular and Medical Genetics in the School of Medicine.
Dr. Adelman's lab continues to utilize these mice to study the role of SK3.
Science. 2000 Sep 15;289(5486):1942-6: Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3.
Circ Res. 2003 Jul 25;93(2):124-31: Altered expression of small-conductance Ca2+-activated K+ (SK3) channels modulates arterial tone and blood pressure.
J Physiol. 2003 Sep 15;551(Pt 3):893-903: Urinary bladder instability induced by selective suppression of the murine small conductance calcium-activated potassium (SK3) channel
J Neurosci. 2004 Jun 9;24(23):5301-6: Small conductance Ca2+-activated K+ channel knock-out mice reveal the identity of calcium-dependent afterhyperpolarization currents.
- OHSU # 0891 B — Small-Conductance CA2+-Activated Potassium Channel 2 (SK2) Transgenic Mice
- OHSU # 0891 — Small-Conductance CA2+-Activated Potassium Channel 1 (SK1) Transgenic Mice
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