Second Mouse Model of Periodic Paralysis Developed

MDA-supported scientists have developed a research mouse with a calcium channel mutation and a disorder that mimics human hypokalemic periodic paralysis

Mice with a mutation in the calcium channel develop a disorder that closely resembles human hypokalemic periodic paralysis.
Article Highlights:
  • A research mouse with a calcium channel mutation — the most common mutation causing human hypokalemic periodic paralysis — has been developed.
  • Last year, a research mouse was developed that has a sodium channel mutation — a less common cause of human hypokalemic periodic paralysis.
  • The mouse models are expected to improve understanding of hypokalemic periodic paralysis and speed development of new treatments for it.
by Margaret Wahl on December 17, 2012 - 5:00am

Scientists supported in part by MDA have developed a second type of research mouse with a disorder mimicking hypokalemic periodic paralysis, a genetic disorder in which recurrent attacks of weakness or paralysis occur in association with low potassium levels in the bloodstream. Like the majority of humans with this disorder, the mice have a mutation in the gene for a muscle-fiber calcium channel, a key player for the initiation of muscle contraction.

This type of "mouse model" of a human disease increases understanding of the disease and enables researchers to screen potential treatments before trying them in humans.

MDA grantee Stephen Cannon

MDA grantee Stephen Cannon, a professor of neurology and neurotherapeutics at the University of Texas Southwestern Medical Center in Dallas, coordinated the study team, which published its findings Dec. 3, 2012, in the Journal of Clinical Investigation. (The paper can be read free of charge.) A commentary about the implications of this and related research is published in the same issue.

In the commentary, Alfred George, professor of pharmacology at Vanderbilt University in Nashville, Tenn., notes that the new mouse model will allow important questions to be addressed, including whether the effects of the genetic mutation on the calcium channel can be blocked to prevent paralysis attacks. George is a former MDA research grantee.

Mouse model has features of human disorder

The genetic mutation the new mice have — known as the calcium channel R528H mutation — is the most common cause of hypokalemic periodic paralysis, the researchers say. It results in a defect in muscle-fiber calcium channels that make the fibers insensitive to stimulation by the nerve impulses when potassium levels are low.

The new mouse "recapitulated all the essential features" of hypokalemic periodic paralysis in humans, the authors write, such as temporary, severe muscle weakness and loss of muscle excitability; and mild permanent weakness of some muscle groups.

This is the second research mouse developed to study this disorder.

Mouse with sodium channel mutation developed last year

Last year, Cannon and colleagues announced they had created the first mouse model of hypokalemic periodic paralysis by developing a mouse with a mutation in the gene for a sodium channel.

Sodium channel gene mutations account for hypokalemic periodic paralysis in 20 percent of families studied so far, while calcium channel mutations account for the disorder in 60 percent. The remaining 20 percent have undetermined mutations.

For more information

To learn more about periodic paralysis, read In Focus: Periodic Paralysis, a Quest article published in July 2009.

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