About This Project

US national reported that 1-2% of students are diagnosed with autism. Autism is difficult to treat because it is based on many subtle mutations in multiple genes. Interestingly, the Mexican cavefish shows traits that are very similar to this disease. The goal of this project is to investigate whether the cavefish's gene expressions are similar to human patients. We will then extract useful information which will facilitate the discovery of new treatment for autism.

Ask the Scientists

What is the context of this research?

Our goal is to promote the findings of new treatments in human autism spectrum disease (ASD) by investigating a new genetic model of the symptoms. ASD is diagnosed in 1-2% of human population, and is difficult to treat because many subtle mutations in genes cause complex reactions in brain development. Current mouse, rat and monkey models face a difficulty to address this multi-genetic point. A new model vertebrate, cavefish, Astyanax mexicanus, is composed of cave-dwelling and an ancestral-type, surface-dwelling populations. This cavefish may complement above mentioned model animals since cavefish shows behavioral and genetic similarities to ASD patients (Yoshizawa et al. soon to be submitted). We are addressing multi-genetic interactions of ASD genes in cavefish.

What is the significance of this project?

ASD research is a highly active-biomedical field. For example, neural cells induced from ASD patient cells (i.e. iPS cell) are used to investigate the defects at the cellular level, such as the synaptic function and cellular metabolism. Also, many mutant mice have been established whose ASDgene is manipulated into malfunctioning. These mutant mice inform the functions of each ASD gene. However, it is difficult to address the mechanisms of perturbation at the neural-circuit level, or at the gene-gene interaction level, with these methods. The cavefish model can fill these knowledge gaps, and has a strong advantage to highlight potential side-effects when the ASD genes are targeted by upcoming gene-targeting treatments (gene-therapy).

What are the goals of the project?

We have narrowed down major cavefish’s candidate genes to 15 by referring to their expression changes at the embryonic stage and their genomic locations, both of which are associated with behavioral/neurological changes (quantitative trait loci for behaviors). We will test whether or not these 15 cavefish genes show similar expressions to the genes in humans during later brain development through quantitative-PCR of cavefish brains.