The zebrafish is well-known for its striking coloring. The animal’s signature black-blue stripes develop over time. Eyelash-sized larvae are transparent. Many developmental processes can be seen under a light microscope. They’re a model organism for researchers around the world.
Prof. Dr. Benjamin Odermatt from the University Hospital Bonn’s Institute of Anatomy studies how zebrafish repair nerve tissue. Many genes involved in this process exist in humans. Agents that boost fish repair genes could work in humans. Fish and humans have different genetic makeups. Larvae have limited use in drug discovery.
Human gene replaces fish gene
Prof. Dr. Evi Kostenis of the University of Bonn‘s Institute of Pharmaceutical Biology explains their approach. “We looked for the zebrafish counterpart of a human nerve-cell-repair gene. We replaced the fish’s counterpart with a human one. ” New DNA replaced the original zebrafish gene. “If we find a substance that boosts repair processes in fish with the human gene, it’s likely to work in humans,” says the researcher at the University of Bonn’s Transdisciplinary Research Area “Life and Health.”
The GPR17 receptor pilot study showed that this replacement works. Overactivation can cause MS in humans (MS). Electrical signals connect nerve cells. Myelin insulates their extensions. It prevents short circuits and speeds up stimulation. Oligodendrocytes create this protective sheath. These resemble a microscopic octopus with many myelin-rich arms. These wrap around developing nerve cells like insulating tape. The protective layer lasts forever.
The insulating tape dispenser remains in an immature state.In MS, the immune system destroys myelin. Speech, vision, and walking are affected. Normal brain repair requires immature oligodendrocytes. They mature and repair damage. In MS, many insulating tape donor cells remain immature. GPR17 receptor activation slows oligodendrocyte maturation.
“Zebrafish have a GPR17 receptor,” says study co-author Dr. Jesus Gomeza. “It also regulates oligodendrocyte maturation.” The researchers replaced part of the receptor gene with its human counterpart, the signal-receiving structure. “This new mosaic gene works normally in fish larvae,” says Gomeza. When the human GPR17 receptor was blocked in a test tube, modified fish made more oligodendrocytes.
Cell cultures are used to test new active ingredients. In mice or other animal models, only promising candidates are tested. Even when they work, human tests are sobering. “Humanized zebrafish larvae allow many substances to be screened quickly and with a high success rate,” says Benjamin Odermatt. They said that “this is a promising drug development avenue
