Accession Number:

ADA592193

Title:

Altered Gastrointestinal Function in the Neuroligin-3 Mouse Model of Autism

Descriptive Note:

Annual rept. 30 Sep 2012-29 Sep 2013

Corporate Author:

MELBOURNE UNIV VICTORIA (AUSTRALIA)

Personal Author(s):

Report Date:

2013-10-01

Pagination or Media Count:

27.0

Abstract:

Up to 80 of ASD patients exhibit gastrointestinal GI problems, but the underlying mechanisms are unknown. Many ASD associated mutations modify synaptic proteins and hence alter synaptic function in the brain. We propose that some of these mutations also alter the enteric nervous system ENS to produce bowel disorders. NL3 mice express a neuroligin-3 mutation identified in ASD patients and are more responsive to the GABA neurotransmission in the brain. This work aims to examine the spatiotemporal distribution patterns of NL3 and related proteins and mRNA in gut tissue from these mice in order to determine biological mechanisms contributing to GI dysfunction in ASD patients. We show expression of synaptic genes CNTNAP2, gephyrin and SHANK3, in mouse enteric tissue and upregulation of genes implicated in ASD and epilepsy during development of the mouse ENS. Neuronal proportions labelled for GABA, nNOS are similar in WT and NL3 adult mouse colon suggesting that the NL3 mutation impacts on synaptic function in the ENS without altering neuronal numbers during development. An unexpected finding from this work is that NL3 is present in presynaptic terminals and should lead to re-evaluation of its location at central synapses.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE