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BMC Biol. 2016 Dec 7;14(1):108.

Sudden death due to paralysis and synaptic and behavioral deficits when Hip14/Zdhhc17 is deleted in adult mice.

Author information

1
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child & Family Research Institute, University of British Columbia (UBC), Vancouver, BC, V5Z 4H4, Canada.
2
Department of Psychiatry, Brain Research Centre and Djavad Mowafaghian Centre for Brain Health, UBC, Vancouver, BC, V6T 1Z3, Canada.
3
Present address: Division of Biomedical Sciences, Faculty of Medicine, Memorial University, Newfoundland and Labrador, A1B 3V6, Canada.
4
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child & Family Research Institute, University of British Columbia (UBC), Vancouver, BC, V5Z 4H4, Canada. mrh@cmmt.ubc.ca.

Abstract

BACKGROUND:

Palmitoylation, the addition of palmitate to proteins by palmitoyl acyltransferases (PATs), is an important regulator of synaptic protein localization and function. Many palmitoylated proteins and PATs have been implicated in neuropsychiatric diseases, including Huntington disease, schizophrenia, amyotrophic lateral sclerosis, Alzheimer disease, and X-linked intellectual disability. HIP14/DHHC17 is the most conserved PAT that palmitoylates many synaptic proteins. Hip14 hypomorphic mice have behavioral and synaptic deficits. However, the phenotype is developmental; thus, a model of post-developmental loss of Hip14 was generated to examine the role of HIP14 in synaptic function in the adult.

RESULTS:

Ten weeks after Hip14 deletion (iHip14 Δ/Δ ), mice die suddenly from rapidly progressive paralysis. Prior to death the mice exhibit motor deficits, increased escape response during tests of anxiety, anhedonia, a symptom indicative of depressive-like behavior, and striatal synaptic deficits, including reduced probability of transmitter release and increased amplitude but decreased frequency of spontaneous post-synaptic currents. The mice also have increased brain weight due to microgliosis and astrogliosis in the cortex.

CONCLUSIONS:

Behavioral changes and electrophysiological measures suggest striatal dysfunction in iHip14 Δ/Δ mice, and increased cortical volume due to astrogliosis and microgliosis suggests a novel role for HIP14 in glia. These data suggest that HIP14 is essential for maintenance of life and neuronal integrity in the adult mouse.

KEYWORDS:

DHHC17; HIP14; Huntington’s disease; Palmitoyl acyltransferase; Palmitoylation

PMID:
27927242
PMCID:
PMC5142322
DOI:
10.1186/s12915-016-0333-7
[Indexed for MEDLINE]
Free PMC Article

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