Comprehensive Behavioral Phenotyping of a 16p11.2 Del Mouse Model for Neurodevelopmental Disorders

Joseph F Lynch III; Sarah L Ferri; Christopher Angelakos; Hannah Schoch; Thomas Nickl-Jockschat; Arnold Gonzalez; William Timothy O'Brien; Ted Abel

doi:10.1002/aur.2357

Journal article

Comprehensive Behavioral Phenotyping of a 16p11.2 Del Mouse Model for Neurodevelopmental Disorders

Joseph F Lynch III, Sarah L Ferri, Christopher Angelakos, Hannah Schoch, Thomas Nickl-Jockschat, Arnold Gonzalez, William Timothy O'Brien and Ted Abel

Autism research, Vol.13(10), pp.1670-1684

10/2020

DOI: 10.1002/aur.2357

PMCID: PMC7990053

PMID: 32857907

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https://www.ncbi.nlm.nih.gov/pmc/articles/7990053View

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Abstract

The microdeletion of copy number variant 16p11.2 is one of the most common genetic mutations associated with neurodevelopmental disorders, such as Autism Spectrum Disorders (ASDs). Here, we describe our comprehensive behavioral phenotyping of the 16p11.2 deletion line developed by Alea Mills on a C57BL/6J and 129S1/SvImJ F1 background (Del ). Male and female Del mice were tested in developmental milestones as preweanlings (PND2-PND12), and were tested in open field activity, elevated zero maze, rotarod, novel object recognition, fear conditioning, social approach, and other measures during post-weaning (PND21), adolescence (PND42), and adulthood (>PND70). Developmentally, Del mice show distinct weight reduction that persists into adulthood. Del males also have reduced grasp reflexes and limb strength during development, but no other reflexive deficits whereas Del females show limb strength deficits and decreased sensitivity to heat. In a modified version of a rotarod task that measures balance and coordinated motor activity, Del males, but not females, show improved performance at high speeds. Del males and females also show age-specific reductions in anxiety-like behavior compared with WTs, but neither sex show deficits in a social preference task. When assessing learning and memory, Del males and females show age-specific impairments in a novel object or spatial object recognition, but no deficits in contextual fear memory. This work extends the understanding of the behavioral phenotypes seen with 16p11.2 deletion by emphasizing age and sex-specific deficits; important variables to consider when studying mouse models for neurodevelopmental disorders. LAY SUMMARY: Autism spectrum disorder is a common neurodevelopmental disorder that causes repetitive behavior and impairments in social interaction and communication. Here, we assess the effects of one of the most common genetic alterations in ASDs, a deletion of one copy of 29 genes, using a mouse model. These animals show differences in behavior between males and females and across ages compared with control animals, including changes in development, cognition, and motor coordination. Autism Res 2020, 13: 1670-1684. © 2020 International Society for Autism Research and Wiley Periodicals LLC.

Phenotype

copy number variant

mouse model

16p11.2

autism spectrum disorders

behavior

neurodevelopmental disorders

Details

Title: Subtitle: Comprehensive Behavioral Phenotyping of a 16p11.2 Del Mouse Model for Neurodevelopmental Disorders
Creators: Joseph F Lynch III - Department of Psychology, Franklin and Marshall College, Lancaster, Pennsylvania, USA
Sarah L Ferri - Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, USA
Christopher Angelakos - Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA
Hannah Schoch - Eison S. Floyd College of Medicine, Washington State University Spokane, Spokane, Washington, USA
Thomas Nickl-Jockschat - Department of Psychiatry, Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, USA
Arnold Gonzalez - Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
William Timothy O'Brien - Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Ted Abel - Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Autism research, Vol.13(10), pp.1670-1684
DOI: 10.1002/aur.2357
PMID: 32857907
PMCID: PMC7990053
NLM abbreviation: Autism Res
ISSN: 1939-3792
eISSN: 1939-3806
Publisher: United States
Grant note: U54 HD086984 / NICHD NIH HHS K01 MH119540 / NIMH NIH HHS
Language: English
Date published: 10/2020
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: 9984070739102771

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