Assessing the validity of current mouse genetic models of obsessive–compulsive disorder

Abstract

Obsessive–compulsive disorder (OCD) is a disorder characterized by unwanted and intrusive thoughts, images, or impulses and/or repetitive behavior. OCD is a major cause of disability; however, the genetic factors and pathophysiological mechanisms underlying this complex, heterogeneous disorder remain largely unknown. During the past decade, a number of putative mouse genetic models of OCD have been developed for the purpose of studying the neural mechanisms underlying this disorder and developing novel treatments. This review presents and evaluates these experimental preparations to date. Models using knockout or transgenic approaches, as well as those examining variation in genetically diverse populations, are evaluated and discussed.

Marble Burying and Nestlet Shredding as Tests of Repetitive, Compulsive-like Behaviors in Mice

“…Both tests show excellent face, construct and predictive validity for the human disorders they model [6][7][8][9][10][11] . These repetitive behaviors are natural and spontaneous in rodents and their frequency and intensity can vary after genetic modifications, as shown presently, or after head injury and treatment of subjects with drugs.…”

“…A large number of animal models of repetitive behaviors as seen in OCD and ASDs have been developed over the past 30 years and numerous excellent reviews describing these models have been published [6][7][8][9][10][11][12][13][14] . In general, these established models can be classified as genetic, pharmacological, neurodevelopmental and behavioral and most show good face, construct and predictive validity 6,7 .…”

Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive–compulsive disorder as an example of overlapping clinical and genetic heterogeneity

“…In rodents, dogs and non-human primates, OCD-like features include perseverative behaviours, compulsive grooming, food restriction-induced compulsive wheel running or drinking, and behaviours such as marble burying [29,[163][164][165] (for reviews, see [161,[166][167][168][169][170]). However, despite 'face validity' and in some instances apparent validity based on biological neurocircuitry involvement or similar drug responses in OCD in humans, few models have implicated specific genes.…”

Dissecting OCD Circuits: From Animal Models to Targeted Treatments

“…Since valid animal models are essential for identifying molecular and cellular events that lead to pathology, substantial effort has gone towards establishing rodent models of OCD 50,51,81 . Though it is generally accepted that no one animal model will be able to recreate all aspects of any complex neuropsychiatric disorder, including OCD 82 , powerful models can nevertheless be generated to recreate particular aspects of a clinical disorder.…”

“…SYMPTOM MODELING-OCD animal models have classically emphasized the presence of stereotyped and compulsive behaviors, although reliance on face validity may lead to discrepancies in the field since identical phenotypes can result from different underlying biological processes (for review see Wang et al, 2009) 81 . These include barbering (repetitive hair biting and pulling), acral paw-lick (repetitive canine paw-licking), zoorelated stereotypies, and marble burying.…”