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

Manoj Kumar; Jeffery T Duda; Wei-Ting Hwang; Charles Kenworthy; Ranjit Ittyerah; Stephen Pickup; Edward S Brodkin; James C Gee; Ted Abel; Harish Poptani

doi:10.1371/journal.pone.0109872

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

Journal article

Open access

Peer reviewed

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

Manoj Kumar, Jeffery T Duda, Wei-Ting Hwang, Charles Kenworthy, Ranjit Ittyerah, Stephen Pickup, Edward S Brodkin, James C Gee, Ted Abel and Harish Poptani

PloS one, Vol.9(10), pp.e109872-e109872

2014

DOI: 10.1371/journal.pone.0109872

PMCID: PMC4192590

PMID: 25299583

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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.

Autism Spectrum Disorder - genetics

Brain - diagnostic imaging

Membrane Proteins - genetics

Humans

Autism Spectrum Disorder - pathology

Autism Spectrum Disorder - diagnostic imaging

Nerve Tissue Proteins - genetics

Cell Adhesion Molecules, Neuronal - genetics

Diffusion Tensor Imaging

Gene Knock-In Techniques

Brain - metabolism

Nerve Tissue Proteins - metabolism

Radiography

Magnetic Resonance Imaging

Animals

Brain - pathology

Cell Adhesion Molecules, Neuronal - metabolism

Membrane Proteins - metabolism

Mice

Mutation

Disease Models, Animal

Details

Title: Subtitle: High resolution magnetic resonance imaging for characterization of the neuroligin-3 knock-in mouse model associated with autism spectrum disorder
Creators: Manoj Kumar - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Jeffery T Duda - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Wei-Ting Hwang - Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Charles Kenworthy - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Ranjit Ittyerah - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Stephen Pickup - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Edward S Brodkin - Center for Neurobiology and Behavior, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
James C Gee - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Ted Abel - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Harish Poptani - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.9(10), pp.e109872-e109872
DOI: 10.1371/journal.pone.0109872
PMID: 25299583
PMCID: PMC4192590
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: R01 MH080718 / NIMH NIH HHS R21 HD058237 / NICHD NIH HHS R01MH080718 / NIMH NIH HHS 5-T32-MH017168 / NIMH NIH HHS R21HD058237 / NICHD NIH HHS T32 MH017168 / NIMH NIH HHS 1P50MH096891 / NIMH NIH HHS P50 MH096891 / NIMH NIH HHS
Language: English
Date published: 2014
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065833102771

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