High resolution magnetic resonance imaging for characterization of the neuroligin-3 knock-in mouse model associated with autism spectrum disorder.

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TitleHigh resolution magnetic resonance imaging for characterization of the neuroligin-3 knock-in mouse model associated with autism spectrum disorder.
Publication TypeJournal Article
Year of Publication2014
AuthorsKumar, M, Duda, JT, Hwang, W-T, Kenworthy, C, Ittyerah, R, Pickup, S, Brodkin, ES, Gee, JC, Abel, T, Poptani, H
JournalPLoS One
Volume9
Issue10
Paginatione109872
Date Published2014
ISSN1932-6203
KeywordsAnimals, Autism Spectrum Disorder, Brain, Cell Adhesion Molecules, Neuronal, Diffusion Tensor Imaging, Disease Models, Animal, Gene Knock-In Techniques, Humans, Magnetic Resonance Imaging, Membrane Proteins, Mice, Mutation, Nerve Tissue Proteins, Radiography
Abstract

Autism spectrum disorders (ASD) comprise an etiologically heterogeneous set of neurodevelopmental disorders. Neuroligin-3 (NL-3) is a cell adhesion protein that mediates synapse development and has been implicated in ASD. We performed ex-vivo high resolution magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI) and behavioral (social approach and zero maze) tests at 3 different time points (30, 50 and 70 days-of-age) on NL-3 and wild-type littermates to assess developmental brain abnormalities in NL-3 mice. MRI data were segmented in 39 different gray and white matter regions. Volumetric measurements, along with DTI indices from these segmented regions were also performed. After controlling for age and gender, the NL-3 knock-in animals demonstrated significantly reduced sociability and lower anxiety-related behavior in comparison to their wild type littermates. Significantly reduced volume of several white and gray matter regions in the NL-3 knock-in mice were also observed after considering age, gender and time point as covariates. These findings suggest that structural changes in the brain of NL-3 mice are induced by the mutation in the NL-3 gene. No significant differences in DTI indices were observed, which suggests that the NL-3 mutation may not have a profound effect on water diffusion as detected by DTI. The volumetric and DTI studies aid in understanding the biology of disrupting function on an ASD risk model and may assist in the development of imaging biomarkers for ASD.

DOI10.1371/journal.pone.0109872
Alternate JournalPLoS One
PubMed ID25299583
PubMed Central IDPMC4192590
Grant ListR21HD058237 / HD / NICHD NIH HHS / United States
P50 MH096891 / MH / NIMH NIH HHS / United States
R01 MH080718 / MH / NIMH NIH HHS / United States
1P50MH096891 / MH / NIMH NIH HHS / United States
T32 MH017168 / MH / NIMH NIH HHS / United States
R01MH080718 / MH / NIMH NIH HHS / United States
5-T32-MH017168 / MH / NIMH NIH HHS / United States
R21 HD058237 / HD / NICHD NIH HHS / United States
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