Journal article
Home-cage hypoactivity in mouse genetic models of autism spectrum disorder
Neurobiology of learning and memory, Vol.165, pp.107000-107000
11/2019
DOI: 10.1016/j.nlm.2019.02.010
PMCID: PMC6913530
PMID: 30797034
Abstract
Genome-wide association and whole exome sequencing studies from Autism Spectrum Disorder (ASD) patient populations have implicated numerous risk factor genes whose mutation or deletion results in significantly increased incidence of ASD. Behavioral studies of monogenic mutant mouse models of ASD-associated genes have been useful for identifying aberrant neural circuitry. However, behavioral results often differ from lab to lab, and studies incorporating both males and females are often not performed despite the significant sex-bias of ASD. In this study, we sought to investigate the simple, passive behavior of home-cage activity monitoring across multiple 24-h days in four different monogenic mouse models of ASD: Shank3b
, Cntnap2
, Pcdh10
, and Fmr1 knockout mice. Relative to sex-matched wildtype (WT) littermates, we discovered significant home-cage hypoactivity, particularly in the dark (active) phase of the light/dark cycle, in male mice of all four ASD-associated transgenic models. For Cntnap2
and Pcdh10
mice, these activity alterations were sex-specific, as female mice did not exhibit home-cage activity differences relative to sex-matched WT controls. These home-cage hypoactivity alterations differ from activity findings previously reported using short-term activity measurements in a novel open field. Despite circadian problems reported in human ASD patients, none of the mouse models studied had alterations in free-running circadian period. Together, these findings highlight a shared phenotype across several monogenic mouse models of ASD, outline the importance of methodology on behavioral interpretation, and in some genetic lines parallel the male-enhanced phenotypic presentation observed in human ASDs.
Details
- Title: Subtitle
- Home-cage hypoactivity in mouse genetic models of autism spectrum disorder
- Creators
- Christopher C Angelakos - Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, United StatesJennifer C Tudor - Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Biology, Saint Joseph's University, Philadelphia, PA 19131, United StatesSarah L Ferri - Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, United States; Molecular Physiology and Biophysics, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242, United StatesThomas A Jongens - Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United StatesTed Abel - Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, United States; Molecular Physiology and Biophysics, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242, United States. Electronic address: ted-abel@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Neurobiology of learning and memory, Vol.165, pp.107000-107000
- Publisher
- United States
- DOI
- 10.1016/j.nlm.2019.02.010
- PMID
- 30797034
- PMCID
- PMC6913530
- ISSN
- 1074-7427
- eISSN
- 1095-9564
- Grant note
- U54 HD086984 / NICHD NIH HHS
- Language
- English
- Date published
- 11/2019
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Psychological and Brain Sciences; Iowa Neuroscience Institute; Developmental and Behavioral Pediatrics; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984070511802771
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