Genetic Modeling Potential Found in Eyeless Fish Species

A cave-dwelling fish that lost its eyes to evolution is becoming a leading model to study diabetes, insomnia, and obesity. A “dream team” of young scientists (Alex Keene, Ph.D., associate professor of biological sciences at FAU’s Charles E. Schmidt College of Science; Johanna Kowalko, Ph.D., assistant professor of biology at FAU’s Harriet L. Wilkes Honors College; and Erik Duboué, Ph.D., principal investigator and assistant professor of biology, also at FAU’s Harriet L. Wilkes Honor College) working together to revolutionize this model system for research has been awarded a $1.1 million NSF EDGE grant to study this unusual fish. About the size of a guppy, the blind Mexican cavefish (Astyanax mexicanus) became trapped in caves hundreds of thousands of years ago, and developed many traits that mimic human disease. 

“I think there’s remarkable potential for this cavefish animal model,” said Keene, director of the Program in Neurogenetics, who first described insomnia in this fish. “One of the most interesting things about this fish model is that they barely sleep and they are obese and diabetic, yet they appear to be completely healthy. The genetic tools that will be developed with this NSF funding might allow us to understand why some humans are highly susceptible to neurological and metabolic disease, while others are resilient.”

Unlike with more commonly used laboratory creatures, the scarcity of available tools to manipulate genes in this species as well as methods for tissue-specific manipulation of function have prevented researchers from using these fish to study gene function. Researchers from Florida Atlantic University along with laboratories at Stowers Institute for Medical Research in Kansas City, the University of Minnesota, and Barr-Ilan University in Israel have received a three-year, National Science Foundation EDGE grant totaling $1,148,464 to address these limitations. Their objective will be the development of powerful transgenic tools and gene-editing technologies in the blind Mexican cavefish to significantly advance it as a research model system.

The establishment of combined tools and stock centers will significantly propel blind Mexican cavefish research and position them as a model for understanding the genetic basis of developmental, behavioral evolution, and human disease. The project will enable research into the molecular mechanisms governing evolved traits and will expand the use of these technologies into diverse biological areas including behavior, physiology and metabolism.

Collaborators on the NSF EDGE award comprise a talented research team that includes not only Keene, Kowalko (who implemented gene editing), and Duboué, but also Suzanne McGaugh, Ph.D., an assistant professor of ecology, evolution and behavior at the University of Minnesota, who sequenced their genome; and Nicolas Rohner, Ph.D., an assistant investigator at the Stowers Institute for Medical Research, who described obesity and diabetes in this model.

The project integrates training for all levels of scientists to enhance science literacy and understanding of genomic advances as well as targeted engagement of public groups ranging from K-12 students to the broader adult community. The team is working with local teachers to develop age-appropriate lessons for active learning to bring cavefish to the classroom. They also are engaging the adult community with a cavefish podcast and will establish a gene-editing course for scientists working on non-model fish systems. Read more details about the program here.

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