Peromyscus maniculatus bairdii as a naturalistic mammalian model of obsessive-compulsive disorder: current status and future challenges

Wolmarans, De Wet; Scheepers, Isabella M.; Stein, Dan J.; Harvey, Brian H.

doi:10.1007/s11011-017-0161-7

Cited by 28 publications

(29 citation statements)

References 140 publications

(221 reference statements)

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“…Regarded collectively, natural compulsive-like behavioural phenotypes expressed by deer mice (Peromyscus maniculatus bairdii), that is large nest building (LNB) and high stereotypy, provide a well-validated naturalistic pre-clinical framework in which to study the etiopathology of OCD (Scheepers, Scheepers, Stein, & Harvey, 2018). Approximately 30% of laboratory housed deer mice of both sexes express LNB (Wolmarans, Stein, & Harvey, 2016).…”

Section: Introductionmentioning

confidence: 99%

Natural compulsive‐like behaviour in the deer mouse (Peromyscus maniculatus bairdii) is associated with altered gut microbiota composition

Scheepers

Cryan

Bastiaanssen

et al. 2019

Eur J of Neuroscience

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Obsessive–compulsive disorder (OCD) is a psychiatric illness that significantly impacts affected patients and available treatments yield suboptimal therapeutic response. Recently, the role of the gut–brain axis (GBA) in psychiatric illness has emerged as a potential target for therapeutic exploration. However, studies concerning the role of the GBA in OCD are limited. To investigate whether a naturally occurring obsessive–compulsive‐like phenotype in a rodent model, that is large nest building in deer mice, is associated with perturbations in the gut microbiome, we investigated and characterised the gut microbiota in specific‐pathogen‐free bred and housed large (LNB) and normal (NNB) nest‐building deer mice of both sexes (n = 11 per group, including three males and eight females). Following baseline characterisation of nest‐building behaviour, a single faecal sample was collected from each animal and the gut microbiota analysed. Our results reveal the overall microbial composition of LNB animals to be distinctly different compared to controls (PERMANOVA p < .05). While no genera were found to be significantly differentially abundant after correcting for multiple comparisons, the normal phenotype showed a higher loading of Prevotella and Anaeroplasma, while the OC phenotype demonstrated a higher loading of Desulfovermiculus, Aestuariispira, Peptococcus and Holdemanella (cut‐off threshold for loading at 0.2 in either the first or second component of the PCA). These findings not only provide proof‐of‐concept for continued investigation of the GBA in OCD, but also highlight a potential underlying aetiological association between alterations in the gut microbiota and the natural development of obsessive–compulsive‐like behaviours.

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Section: Introductionmentioning

confidence: 99%

Natural compulsive‐like behaviour in the deer mouse (Peromyscus maniculatus bairdii) is associated with altered gut microbiota composition

Scheepers

Cryan

Bastiaanssen

et al. 2019

Eur J of Neuroscience

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“…In contrast, there are 63 GO terms that are underrepresented in the list, including sensory perception of smell, sensory perception of chemical stimulus, sensory perception, G protein-coupled receptor signaling pathway, and nervous system process, suggesting that these biological processes are more conserved between the two species. (15). BW animals are also less social than PO animals, another hallmark of autism in humans (13,22).…”

Section: Analysis Of Genomic Variations Between P Maniculatus and Pmentioning

confidence: 99%

“…For instance, The BW stock of P. maniculatus has a high incidence of repetitive behavior, while the PO stock of P. polionotus has no repetitive behavior (13,14). In humans, repetitive behavior is observed in people with autism and obsessive-compulsive disorder (15). A QTL analysis for repetitive behavior using P. maniculatus and P. polionotus hybrids could identify the genetic loci associated with this behavior and provide an animal model for understanding complex behaviors associated with human disease.…”

Section: Introductionmentioning

confidence: 99%

Using Genomic Resources for Linkage Analysis in Peromyscus with an Application for Characterizing Dominant Spot

Shang

Horovitz

McKenzie

et al. 2020

Preprint

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Background: Peromyscus are the most common mammalian species in North America and are widely used in both laboratory and field studies. The deer mouse, P. maniculatus and the old-field mouse, P. polionotus, are closely related and can generate viable and fertile hybrid offspring. The ability to generate hybrid offspring, coupled with developing genomic resources, enables researchers to conduct linkage analysis studies to identify genomic loci associated with specific traits. Results: We used available genomic data to identify DNA polymorphisms between P. maniculatus and P. polionotus and used the polymorphic data to identify the range of genetic complexity that underlies physiological and behavioral differences between the species, including cholesterol metabolism and genes associated with autism. In addition, we used the polymorphic data to conduct a candidate gene linkage analysis for the Dominant spot trait and determined that Dominant spot is linked to a region of chromosome 20 that contains a strong candidate gene, Sox10. During the linkage analysis, we found that the spot size varied quantitively in affected Peromyscus based on genetic background. Conclusions: The expanding genomic resources for Peromyscus facilitate their use in linkage analysis studies, enabling the identification of loci associated with specific traits. More specifically, we have linked a coat color spotting phenotype, Dominant spot, with Sox10, a member the neural crest gene regulatory network, and that there are likely two genetic modifiers that interact with Dominant spot. These results establish Peromyscus as a model system for identifying new alleles of the neural crest gene regulatory network.

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“…There are strong parallels between OCD and other ARB-related conditions, and animal models of OCD proposed based on their phenotypic stereotypy profiles, include genetic models (e.g., hyperdopaminergic mutant deer mice [137,138] and Sapap, Slitrk5 and HoxB8 knockout mice [139]), druginduced and some other models [43,140,141]. Zebrafish models of OCD are gaining value in neuropsychiatric research [142][143][144][145].…”

Section: Modeling Obsessive-compulsive Disorder In Zebrafishmentioning

confidence: 99%

“…Paralleling clinical findings, several rodent models with overt spontaneous stereotypies (e.g. deer mice, BTBR T+tf/J, C57BL/10, C57BL/6, C58 mice) are widely used to study ARBs, in which affected animals display repetitive jumping and self-grooming [40][41][42][43]. Neurochemical and clinical volumetric studies of the basal ganglia pathways implicate all major neurotransmitters in ARBs [44].…”

Section: Introductionmentioning

confidence: 99%

Abnormal repetitive behaviors in zebrafish and their relevance to human brain disorders

Zabegalov

Khatsko

Lakstygal

et al. 2019

Behavioural Brain Research

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Abnormal repetitive behaviors (ARBs) are a prominent symptom of numerous human brain disorders and are commonly seen in rodent models. As rodent studies of ARBs continue to dominate the field, mounting evidence suggests that zebrafish (Danio rerio) also display ARB-like phenotypes and may therefore be a novel model organism for ARB research. In addition to practical research advantages, zebrafish share high genetic and physiological homology to humans and rodents, including multiple ARB-related genes and stereotypic behaviors relevant to ARB. Here, we discuss a wide spectrum of stereotypic repetitive behaviors in zebrafish, data on their genetic and pharmacological modulation, and the overall translational relevance of fish ARBs to modeling human brain disorders. Overall, the zebrafish is rapidly emerging as a new promising model to study ARBs and their underlying mechanisms.

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Peromyscus maniculatus bairdii as a naturalistic mammalian model of obsessive-compulsive disorder: current status and future challenges

Cited by 28 publications

References 140 publications

Natural compulsive‐like behaviour in the deer mouse (Peromyscus maniculatus bairdii) is associated with altered gut microbiota composition

Natural compulsive‐like behaviour in the deer mouse (Peromyscus maniculatus bairdii) is associated with altered gut microbiota composition

Using Genomic Resources for Linkage Analysis in Peromyscus with an Application for Characterizing Dominant Spot

Abnormal repetitive behaviors in zebrafish and their relevance to human brain disorders

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