Table of Contents

Viewpoints

• • Bart M. G. Smits and
  • Michael N. Gould

  “Gene Targeting in the Rat? Cut it out!”

  Mol Interv October 2009 9:226-229; doi:10.1124/mi.9.5.5
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  In the last decade, use of the rat as a genetic model has gained significance. Unfortunately, the great advances that have been achieved through the genetic manipulation of mice have not been achieved through attempts to manipulate the rat genome. However, Geurts and colleagues have recently made an important contribution to the genetic toolbox as applied to the rat system. Using zinc-finger nuclease (ZFN) technology, they successfully targeted the rat genome, creating gene knockouts. The reported efficiency of the procedure in producing targeted alleles is surprisingly high. This technology will likely become the gold standard for targeted gene disruption in the rat and will undoubtedly revolutionize rat genetic research. The question remains whether the ZFN technology will also expedite the development of targeted gene replacement (“knock-in”) rat models.

• • Li Pang and
  • Nancy J. Rusch

  High-conductance, Ca²⁺-activated K⁺ Channels: Altered Expression Profiles in Aging and Cardiovascular Disease

  Mol Interv October 2009 9:230-233; doi:10.1124/mi.9.5.6
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  The high-conductance, Ca²⁺-activated K⁺ (BK) channel in vascular smooth muscle cells (VSMCs) exerts a vasodilator influence that buffers vascular tone. There is strong evidence that abnormalities in the number or activity level of the BK channels can trigger vasoconstriction, disrupt blood flow to critical organs and elevate blood pressure. Indeed, a loss of BK channels has been detected in conditions associated with accentuated vascular tone, including aging, metabolic syndrome, diabetes, and some forms of hypertension. In these conditions, the homeostatic efforts of the vasculature to retain normal vascular tone may be compromised by a reduced number of BK channels and by a loss of the endothelium-derived vasodilator factors that promote channel opening. Owing to its recognized role in mediating vasodilation, the BK channel is regarded as a therapeutic target for the treatment of aging and age-related cardiovascular diseases that are associated with abnormal vascular tone.