Article abstract
Nature Neuroscience 11, 1302 - 1310 (2008)
Published online: 5 October 2008 | doi:10.1038/nn.2204
Palmitoylation-dependent neurodevelopmental deficits in a mouse model of 22q11 microdeletion
Jun Mukai1, Alefiya Dhilla2, Liam J Drew1, Kimberly L Stark3, Luxiang Cao1, Amy B MacDermott1,4, Maria Karayiorgou3 & Joseph A Gogos1,4
Abstract
Individuals with 22q11.2 microdeletions have cognitive deficits and a high risk of developing schizophrenia. Here we provide evidence that primary hippocampal neurons from a mouse model of 22q11.2 deletion (Df(16)A+/- mice) have decreased density of dendritic spines and glutamatergic synapses, as well as impaired dendritic growth. These deficits were prevented by introduction of the enzymatically active ZDHHC8 palmitoyltransferase encoded by a gene in the 22q11.2 locus, and they were also observed in primary cultures from Zdhhc8-deficient mice. Many of these deficits were also present in the hippocampi of adult Df(16)A+/- and Zdhhc8-deficient mice. Finally, we provide evidence that PSD95 is one of the substrates of ZDHHC8. Our analysis reveals that 22q11.2 microdeletion results in deficits in neuronal development and suggests that impaired neuronal protein palmitoylation contributes to many of these deficits.
- Department of Physiology and Cellular Biophysics, Columbia University, 630 West 168th Street, New York, New York 10032, USA.
- Department of Pharmacology, College of Physicians & Surgeons, Columbia University, 630 West 168th Street, New York, New York 10032, USA.
- Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, New York 10032, USA.
- Department of Neuroscience, College of Physicians & Surgeons, Columbia University, 1051 Riverside Drive, New York, New York 10032, USA.
Correspondence to: Maria Karayiorgou3 e-mail: mk2758@columbia.edu
Correspondence to: Joseph A Gogos1,4 e-mail: jag90@columbia.edu
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