Pigs, jellyfish and zebrafish don't seem to have much in common with each other, much less humans, but the different species are all pieces of a puzzle which is helping to solve the riddles of diseases in humans - like hereditary forms of diseases affecting the nervous system, such as Parkinson's disease, Alzheimer's disease, autism, epilepsy and the motor neurone disease ALS.
In a new project, Aarhus University scientists focused on a specific gene in pigs. The gene, SYN1, encodes the protein synapsin, which is involved in communication between nerve cells. Synapsin almost exclusively occurs in nerve cells in the brain. Parts of the gene can thus be used to control an expression of genes connected to hereditary versions of the aforementioned disorders.
The SYN1 gene can, with its specific expression in nerve cells, be used for generation of pig models of neurodegenerative diseases like Parkinson's. The reason scientists bring a pig into the equation is that the pig is well suited as a model for investigating human diseases.
"Pigs are very like humans in their size, genetics, anatomy and physiology. There are plenty of them, so they are easily obtainable for research purposes, and it is ethically easier to use them than, for example, apes," says senior scientist Knud Larsen from Aarhus University.
Before the gene was transferred from humans to pigs, the scientists had to ensure that the SYN1 gene was only expressed in nerve cells. This was where the zebra fish entered the equation.
The zebrafish and the jellyfish
"The zebrafish is, as a model organism, the darling of researchers, because it is transparent and easy to genetically modify. We thus attached the relevant gene, SYN1, to a gene from a jellyfish (GFP), and put it into a zebrafish in order to test the specificity of the gene," explains Larsen.
That is because jellyfish contain a gene that enables them to light up. This gene was transferred to the zebrafish alongside SYN1, so that the scientists could follow where in the fish activity occurred as a result of the SYN1 gene.
"We could clearly see that the transparent zebrafish shone green in its nervous system as a result of the SYN1 gene from humans initiating processes in the nervous system. We could thus conclude that SYN1 works specifically in nerve cells," he says.
The results of this investigation pave the way for the SYN1 gene being used in pig models for research into human diseases. The pig with the human gene SYN1 can presumably also be used for research into the development of the brain and nervous system in the foetus.
"I think it is interesting that the nervous system is so well preserved, from an evolutionary point of view, that you can observe a nerve-cell-specific expression of a pig gene in a zebrafish. It is impressive that something that works in a pig also works in a fish."