Now an assistant professor of biomedical sciences in Cornell's veterinary college, Xin was a postdoctoral researcher in Vanderbilt's Department of Biological Sciences when he developed the so-called knock-out mouse (or null mouse) that lacks the gene to produce the binding protein FKBP12.6. The protein is associated with receptors in heart muscle cells that signal for the contraction of muscle cells when calcium ions pass through channels, causing the heart to pump blood.
The Cornell-Vanderbilt mouse studies show for the first time how FKBP12.6 regulates the release of calcium in muscle-cell signaling, and also suggested that estrogen can protect mice -- and perhaps humans, too -- from the consequences of poorly regulated calcium release.
"When we examined calcium release in heart cells from knock-out mice, we found an abnormal calcium release process in both male and female mice," Kotlikoff says. "Calcium-release events were lengthened and increased in size in knock-out mice," he says, describing a kind of calcium overload to the signaling channels. "This is the first demonstration that FKBP12.6 participates in excitation/contraction coupling in the normal heart."
More surprising to the researchers, however, was the difference between male and female mice, both lacking the gene for FKBP12.6. Even though heart cells in female and male mice had the same genetic defect and the same degree of abnormal calcium release, females were somehow protected from developing cardiac enlargement in response to the defect.
"We wondered whether the factor protecting t
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Contact: Roger Segelken
hrs2@cornell.edu
607-255-9736
Cornell University News Service
22-Mar-2002