Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders

Ku, Katherine; Weir, Ruth K.; Silverman, Jill L.; Berman, Robert F.; Bauman, Melissa D.

doi:10.1371/journal.pone.0158150

Cited by 67 publications

(40 citation statements)

References 93 publications

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“…The enhanced social repertoire and strain specific differences of the rat model (74) may provide a test bed to evaluate the effects of MIA on social development, though early social interactions have not been thoroughly characterized in the rat MIA model (75). Preliminary evidence also suggests that the nonhuman primate may provide a valuable tool to bridge the gap between rodent models and patient populations.…”

Section: Assessing Validity Of the Mia Modelmentioning

confidence: 99%

Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates

Careaga

Murai

Bauman

2017

Biological Psychiatry

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284

199

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A subset of women who are exposed to infection during pregnancy have an increased risk of giving birth to a child who will later be diagnosed with a neurodevelopmental or neuropsychiatric disorder. Although epidemiology studies have primarily focused on the association between maternal infection and an increased risk of offspring schizophrenia (SZ), mounting evidence indicates that maternal infection may also increase the risk of autism spectrum disorder (ASD). A number of factors, including genetic susceptibility, the intensity and timing of the infection, and exposure to additional aversive postnatal events, may influence the extent to which maternal infection alters fetal brain development and which disease phenotype (ASD; SZ; other neurodevelopmental disorders) is expressed. Preclinical animal models provide a test bed to systematically evaluate the effects of maternal infection on fetal brain development, determine the relevance to human CNS disorders, and to evaluate novel preventative and therapeutic strategies. Maternal immune activation (MIA) models in mice, rats, and nonhuman primates suggest that the maternal immune response is the critical link between exposure to infection during pregnancy and subsequent changes in brain and behavioral development of offspring. However, differences in the type, severity, and timing of prenatal immune challenge paired with inconsistencies in behavioral phenotyping approaches have hindered the translation of preclinical results to human studies. Here we highlight the promises and limitations of the MIA model as a preclinical tool to study prenatal risk factors for ASD, and suggest specific changes to improve reproducibility and maximize translational potential.

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Section: Assessing Validity Of the Mia Modelmentioning

confidence: 99%

Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates

Careaga

Murai

Bauman

2017

Biological Psychiatry

Self Cite

284

199

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“…Rats were exposed to a 100 cm square three-chamber sociability apparatus (Noldus) containing empty wire cages in the corners of each of the lateral chambers similar to previously described methods [Ku, Weir, Silverman, Berman, & Bauman, 2016;Yang, Silverman, & Crawley, 2011]. Rats at 3-4 months of age (AS male n = 6, AS female n = 10, WT male n = 9, WT female n = 6) were acclimated to the device for two trials lasting 5 min with a 15 min inter-trial interval.…”

Section: Social Approachmentioning

confidence: 99%

Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion

et al. 2020

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Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, lack of speech, and ataxia. The gene responsible for AS was identified as Ube3a and it encodes for E6AP, an E3 ubiquitin ligase. Currently, there is very little known about E6AP's mechanism of action in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. Elucidating the mechanistic action of E6AP would enhance our understanding of AS and drive current research into new avenues that could lead to novel therapeutic approaches that target E6AP's various functions. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat phenotypically mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. Autism Res 2020, 13: 397–409. © 2020 International Society for Autism Research,Wiley Periodicals, Inc. Lay Summary Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, difficulty speaking, and ataxia. The gene responsible for AS was identified as UBE3A, yet very little is known about its function in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS.

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“…Three-chambered social approach. Social approach using a three-chambered apparatus was measured by methodology similar to protocols described previously for mice [Silverman, Yang, Lord, & Crawley, 2010;Yang, Silverman, & Crawley, 2011;Silverman et al, 2012;Sukoff Rizzo & Silverman, 2016;Dhamne et al, 2017] and rats [Ku et al, 2016] with modifications outlined in the Supporting Methods.…”

Section: Behavioral Assaysmentioning

confidence: 99%

“…Open field locomotion. Exploratory activity in a novel open arena was evaluated as described previously [Ku et al, 2016], in order to control for potentially confounding effects of sedation or hyperactivity on the sociability assays.…”

Section: Behavioral Assaysmentioning

confidence: 99%

Developmental social communication deficits in the Shank3 rat model of phelan‐mcdermid syndrome and autism spectrum disorder

et al. 2018

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Clinically relevant outcomes are required to demonstrate the utility of therapeutics. We introduce findings in a rat model, and assess the impact of mutations in Shank3, an autism risk gene. We found that males with deficient expression of Shank3 did not demonstrate typical responses in a bi-directional social communication test and that social interaction was lower on key parameters. Outcome measures reported herein extend earlier results in mice and capture responses to acoustic calls, which is analogous to measuring receptive and expressive communication.

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Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders

Cited by 67 publications

References 93 publications

Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates

Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates

Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion

Developmental social communication deficits in the Shank3 rat model of phelan‐mcdermid syndrome and autism spectrum disorder

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