Birth defect gene linked to mental illness in mouse study

Gene
mutations that can cause major birth defects may also cause more subtle
disruptions in the brain and contribute to psychiatric disorders, according to a study.

Researchers investigated the function of the Dact1 gene, which is involved in
the formation of the nervous system and plays an important role in embryonic
development. Dact1 mutations are known to cause a range of severe spinal cord
and brain malformations in mice, some resembling the human condition spina
bifida.

The team deleted Dact1 gene function in the brains of mice and found that nerve formation was
affected, causing neuron growth and branching similar to that seen in mice with models of psychiatric disorders.

'When you delete this gene function after initial, early development — just eliminating
it in neurons after they've formed — they migrate to the right place and their
numbers are correct, but their morphology is a little off', said Dr Benjamin
Cheyette at the University of California, San Francisco, who led the study. 'And that's
very much in line with the kinds of pathology that people have been able to
identify in psychiatric illness'.

The
researchers deleted the Dact1 protein in just one group of nerve cells in the
brain known as cortical interneurons. The genetically altered interneurons,
despite being relatively normal in size and number and in the correct position
in the brain, had significantly fewer synapses, connections with other nerve
cells, and did not branch out in the same way as cells with normal Dact1
function.

Cortical interneurons
regulate activity in the cerebral cortex, including cognitive and sensory
processes. Poor function of interneurons has been linked to several psychiatric
conditions, including autism, schizophrenia and bipolar disorder.

The group
are conducting research into the Wnt pathway, a cell signalling pathway that the
Dact1 gene affects, in people with autism. The team also plan to perform behavioural
experiments with the mice to test whether they have abnormalities in
sociability, sensory perception, anxiety or motivation that resemble symptoms
in major psychiatric disorders.