Cornell researchers have genetically engineered mice whose hearts glow with a green light every time they beat.
The development gives researchers insights into how hearts develop in living mouse embryos and could improve our understanding of irregular heartbeats, known as arrhythmias, as well as open doors to observing cellular processes to better understand basic physiology and disease.
The technique for making living, functional cells fluoresce, or glow, when the concentration of calcium ions rise within cells, is described online in the Proceedings of the National Academy of Sciences.
"The proteins act as molecular spies that tell us what is happening within cells in the living mouse," said Michael Kotlikoff, professor and chair of the Department of Biomedical Sciences at Cornell's College of Veterinary Medicine.
Cornell researchers are breeding new lines of mice with similar proteins that target neurons in the brain, in parasympathetic nerves, in blood vessels or in Purkinje fibers, which prompt the heart's ventricles to pump. The researchers have also transplanted cells from the mice with glowing hearts into normal mice to see whether the transplanted cells function normally within the host heart, which could offer insights for heart repair.
In the study, 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.
Calcium turns the sensor molecule off and on like a molecular switch. Greater fluorescence indicates higher calcium levels, and the sensor shows the patterns, rate and force of heart contractions.
Since the mouse heart beats approximately 6 to 10 times per second, imaging requires a special high-speed camera that is cooled to minus 90 degrees Celsius (minus 128 Fahrenheit), reducing "noise" for a sharper image. Co-author Guy Salama of the University of Pittsburgh contributed the optical imaging work.