title: High resolution magnetic resonance imaging for characterization of the neuroligin-3 knock-in mouse model associated with autism spectrum disorder.
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.
authors.affiliation: Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jeffery T
authors.initials: JT
authors.lastname: Duda
authors.affiliation: 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.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hwang
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Kenworthy
authors.affiliation: Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Ittyerah
authors.affiliation: Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Pickup
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Brodkin
authors.affiliation: Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: James C
authors.initials: JC
authors.lastname: Gee
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ted
authors.initials: T
authors.lastname: Abel
authors.affiliation: Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Harish
authors.initials: H
authors.lastname: Poptani
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D055879:Gene Knock-In Techniques; D006801:Humans; D008279:Magnetic Resonance Imaging; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011859:Radiography
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C098004:neuroligin 3