Technologies

Summary

Treatments for schizophrenia are currently lacking, even though it affects 1% of the population globally. This technology is a mouse model of the human ZDHHC8 gene. The deletion of this gene is known to be the leading cause of nonfamilial schizophrenia. Genetic variance in this gene causes a defect in neuron structure and brain function that most commonly manifests as schizophrenia. This technology may provide a route towards effective schizophrenia therapies.

An accurate genetic model of schizophrenia leads to more successful treatment strategies

Currently, there is a lack of drug development for schizophrenia; previous attempts ended in failure because of the lack of an evidence-based approach. This technology is a well-defined mouse model of nonfamilial schizophrenia. The ZDHHC8 gene encodes a palmitoyltransferase that is essential for proper neuron growth. Deficiency in this protein causes disruption of neuronal axon growth, and manifests in schizophrenia-like behavior in mice and humans. Replacement of this enzyme was shown to normalize behavior and may lead to a potential therapeutic approach.

Tech Ventures Reference: IR CU15276

Publications

• Mukai J, Liu H, Burt RA, Swor D, Lai W-S, Karayiorgou M & Gogos JA. Evidence that the gene encoding ZDHHC8 contributes to the risk of the 22q11-associated schizophrenia. Nature Genetics 36, 725-31 (2004).




• Mukai J, Dhilla A, Drew LJ, Stark KL, Cao L, MacDermott AB, Karayiorgou M & Gogos JA. Palmitoylation-dependent neurodevelopmental deficits in a mouse model of 22q11 microdeletion. Nature Neuroscience 11, 1302-10 (2008).




• Mukai J, Tamura M, Fénelon K, Rosen AM, Spellman TJ, Kang R, MacDermott AB, Karayiorgou M, Gordon JA, Gogos JA. Molecular substrates of altered axonal growth and brain connectivity in a mouse model of schizophrenia. Neuron 86, 680-95 (2015).