Mice with glowing hearts to help us
In an attempt to better understand human irregular heartbeats (or arrhythmias), Japanese and U.S. researchers have genetically engineered mice with glowing hearts. Every time their hearts beat, a green light is emitted. The researchers achieved this result by increasing the concentration of calcium ions within living mouse embryos. "Using this technique, the researchers were able to track the embryo's developing heart to glean insights into how the heart forms." It's not the first time that researchers have used glowing mice, but previous trials were more focused on finding remedies than to understand how the heart starts to beat. But read more...
Here is an introduction from the Cornell Chronicle about the work done by Michael Kotlikoff and his colleagues around the globe.
In the study [to be published by the Proceedings of the National Academy of Sciences,] the mouse was engineered to express a specially designed molecule that fluoresces when calcium, which increases dramatically with each muscle contraction, is released in heart cells. Co-author Junichi Nakai of the RIKEN Brain Science Institute in Wako-shi, Japan, developed the fluorescent molecule by modifying a green fluorescent protein (derived from bioluminescent jellyfish) and making it glow brightly enough to be observed in the working heart.
Below is a series of pictures showing the growth of a mouse heart (Credit: Michael Kotlikoff et al.). "This series reveals increases in cell calcium from a mouse embryo's upper heart through the lower heart on day 10 of development. Cell calcium rises when muscles contract. The bottom row shows a dramatic slowing of the conducted calcium wave between the upper and lower heart chambers."
What is more fascinating in this story -- at least for me -- is that how the heart is growing.
"We knew that the heart starts to pump at around 9.5 days," said Kotlikoff. By day 10.5, there are only two chambers (rather than four chambers in an adult mammal): an atrium on top and a ventricle on the bottom. A delay in beats between the two gives the atrium time to contract and push blood through the heart, but the mechanism that controls that signal, the atrio-ventricular node (AV node), doesn't develop until day 13. Nobody knew how the heart coordinated the pumping without this key component.
And the researchers discovered the reason for this delay.
Using the new technique, which tracks the rise of calcium as the heart muscle contracts, the researchers discovered a layer of specialized cells on the surface of the developing heart that delays the beating between the upper to lower parts of the heart. After 13.5 days of development, the two portions of the heart separate into four, and there is a functional AV node. By that time, the technique revealed, the specialized cells have died so that functions are not duplicated.
As I mentioned above, glowing mice are not that new. For another example, you can read about a collaboration between Chinese and U.S. researchers, "Glowing mice to speed up cancer research."
And if you're interested by glowing mice, you also can read "Glowing hearts shine light on heart disease," a project from Vanderbilt University Medical Center.
For even more information, this research was published by Nature Medicine under the title "Calmodulin kinase II inhibition protects against structural heart disease" on March 27, 2005. Here are two links to the abstract and to the full paper.
Sources: Krishna Ramanujan, Cornell Chronicle, March 7, 2006; and various web sites
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