Ithaca, New York (04/26/06)- Researchers have found a way to make
mouse hearts glow green each time they beat. The feat was accomplished by
creating genetically altered mice by modifying and inserting a gene from
a jellyfish known for its ability to fluoresce. Not only that, researchers
can turn
the
glowing feature on and off, at will.
But
this is
more than just a party trick. The reason for having such a mouse
is so that specific features of beating hearts can be studied. In
this case, the fluorescence is associated with changes in calcium levels
at the cellular level, and so allows researchers to observe these changes
in
living, beating hearts, according to Michael Kotlikoff,
PhD, professor and chair of the department of biomedical sciences
at the College of Veterinary
Medicine at Cornell University.
Calcium levels increase when heart cells contract, and decrease when the
cells relax. "The fluorescence is proportional to the level of calcium
in the cell," he told Access Excellence. "Every time the heart
beats, all the cells in the heart sequentially release calcium and calcium
goes up about ten-fold within the cell." Changes in fluorescence
are recorded through use of a specially designed high-speed digital video
camera.
Fluorescing hearts can be observed in adult mice as well as ones that
are still in embryonic form. "The heart is unique in that it's
the first organ that functions in the body and it has to function before
it's completely developed," he said. In the embryonic
mouse,
cells that form the heart start to beat even before
the heart is fully developed.
While this is already a well established fact, there are still a lot of unanswered
questions about how those cells combine with each other and morph into a
fully developed heart.
The ability to track changes in levels of a chemical such as calcium gives
researchers a tool they can use to study the biology of the heart, and
gather information about what happens when cells communicate with each
other.
There is a lot of complex biology that can't be studied with a single
cell on a microscope slide. Scientists want to learn what happens
when various cells interact with each other; things such as nerves interacting
with muscles, or vessels interacting with their surrounding environment.
"It's the signals between those cells that we're interested in eavesdropping
on.
And it's through genetic engineering that this
can be done in a stable way," he said. "It really opens a new
window in biology and tells us about complex events that we have no other
way of knowing about."
The project is exciting because until now there haven't been effective
ways to observe chemical changes in live, beating
hearts, Dr. Kotlikoff said.
"Now, we have molecular-scale signals that we can record in vivo, in
live working
hearts. There's no other way to do this, other than genetically. (Otherwise
we have to) take the heart out, take apart all the cells and load them with
dye just to measure calcium in individual cells...What I really
want to see is how those cells are talking to each other – what the
overall event is," he said.
The gene used in the study was derived from the green
fluorescent protein (GFP) found in the Aequorea jellyfish. The researchers
altered the gene so that the protein it produced would bind and respond
to calcium. The
gene was also designed so it could be turned off. This is done by giving
the genetically altered mice a compound (in this case a common antibiotic)
that blocks the expression of the GFP gene. When the antibiotic wears off,
the heart cells start to fluoresce again.
The researchers are also creating other kinds of fluorescing genes to detect
other chemicals besides calcium in order to study tissue repair, cell function
and more. The study was published recently in Proceedings
of the National Academy of Sciences (PNAS 2006 103:4753-4758).
end
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