Name: marble burying and nestlet shredding as tests of repetitive, compulsive-like behaviors in mice
Uploaded: 2013-12-24T13:45:00.000+00:00
Duration: 6 min 50 s
Description: Watch this Scientific Journal Video about Marble Burying and Nestlet Shredding as Tests of Repetitive, Compulsive-like Behaviors in Mice at JoVE.com

This work was supported by grants from the Department of Veterans Affairs and the National Institutes of Health.

All protocols using animals were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocols were approved by the Institutional Care and Use Committee of Wayne State University (Permit Number A3310-01).
1.&#160;Preparation of Cages for Marble Burying and Nestlet Shredding
<ol>
	<li>Use standard polycarbonate rat cages (26 cm x 48 cm x 20 cm) with fitted filter-top covers for the marble burying test. Add fresh, unscented mouse bedding material to each cage to a depth of 5 cm and level bedding surface by inserting another cage of the same size onto the surface of the bedding. This has the added advantage of impressing a template of parallel lines on the bedding surface that can be used for marble placement.</li>
	<li>Place standard glass toy marbles (assorted styles and colors, 15 mm diameter, 5.2 g in weight) gently on the surface of the bedding in 5 rows of 4 marbles (see Figure 1A). Wash marbles in mild laboratory detergent, rinse exhaustively in distilled-deionized water, and dry prior to each use.</li>
	<li>Use standard polycarbonate rat cages (19 cm &#160;x 29 cm x 13 cm) with fitted filter-top covers for the nestlet shredding test. Add fresh, unscented mouse bedding material to each cage to a depth of 0.5 cm and pack bedding by insertion of another cage of the same size onto the surface of the bedding.</li>
	<li>Weigh commercially available cotton fiber nestlets (5 cm x 5 cm, 5 mm thick, ~2.5 g each) on an analytical balance and place one nestlet is placed on top of the bedding in each test cage (see Figure 3A).</li>
	<li>Set stop watches or timers for timing session lengths (30 min for each test).</li>
</ol>
2.&#160;Animal Handling Prior to Testing
<ol>
	<li>House mice individually or in groups in a room with a 12 hr light/dark cycle. Provide all mice with food and water ad libitum. Handle mice gently for three to five days prior to testing. Use mice of either sex for both tests.</li>
	<li>Perform behavioral testing between 9:00 am and 4:00 pm and transport all home cages containing mice to the testing room 60 min before the start of testing.</li>
</ol>
3.&#160;Marble Burying Test
<ol>
	<li>Place one mouse into a corner of the cage containing marbles, being careful to place the mouse on bedding as far from marbles as possible, and place the filter-top cover on the cage. Withhold food and water during the test. Allow mouse to remain in the cage undisturbed for 30 min.</li>
	<li>Remove the mouse and return it to its home cage after test completion, taking extreme care not to move or dislodge the marbles in the process of removing the subject from the cage.</li>
	<li>Task scorers (2-3) blind to the treatment conditions or genotype of the mouse being tested to count the number of marbles buried. Score a marble as buried if two-thirds of its surface area is covered by bedding. Average scores for the number of marbles buried for each mouse.</li>
	<li>Retrieve all 20 marbles from the bedding. Dispose of bedding.</li>
</ol>
4.&#160;Nestlet Shredding Test
<ol>
	<li>Place one mouse into a cage containing a single, preweighed nestlet and place the filter-top cover on the cage. Withhold food and water during the test. Leave mouse undisturbed in the cage with the nestlet for 30 min.</li>
	<li>Remove mouse and return to it to its home cage after test completion. Remove the remaining intact nestlet material from the cage with forceps and allow to dry O/N.</li>
	<li>Weigh remaining unshredded nestlet and divide this weight by the starting weight to calculate percentage&#160;of nestlet shredded. If desired, score the form of the nest produced by the subject mouse using a definitive 5-point nest rating scale17 but realizing that this scale is generally intended for scoring nest building, not obsessive-like shredding.</li>
	<li>Discard remaining shredded nestlet material and bedding.</li>
</ol>

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The authors declare that they have no competing financial interests.

The marble burying and nestlet shredding tests are good examples of behavioral methods for studying repetitive and compulsive-like behaviors in mice. Both tests show excellent face, construct and predictive validity for the human disorders they model6-11. 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. The value of these two tests derives from ...

Mouse models of human behaviors, and particularly psychiatric disorders, constitute important and essential experimental approaches to the study of disease mechanisms and to the development of new therapies. Many psychiatric illnesses remain extremely difficult to model in animals (e.g.&#160;schizophrenia). However, animals exhibit a large number of natural and distinctive behaviors that can readily be linked to similar behaviors in humans. Movement or locomotor activity is one example of a behavior in animals that has a counterpart in humans. Rodents often engage in a variety of repetitive behaviors and examples include grooming or digging. One psychiatric condition that involves the exhibition of recurrent and unwanted behaviors in humans is obsessive-compulsive disorder (OCD). Behaviors that are highly characteristic of OCD include checking, counting, and excessive washing or grooming. OCD is a highly prevalent (affects 1-3% of the population) and debilitating psychiatric disorder1. A large number of pharmacological and behavioral approaches have been used to treat OCD. Many of these fall short of providing long-term relief and relapse is common at the end of a treatment regimen2,3. Another psychiatric condition that involves the expression repetitive behaviors is autism spectrum disorder (ASD). ASDs are characterized by deficits in communication and social interaction&#160;and repetitive, stereotyped behaviors to include spinning, rocking, finger flicking&#160;or flapping, and complex body movements. The Centers for Disease Control and Prevention has estimated that about 1 in 88 children are diagnosed with ASDs. Treatment options for this disorder are extremely limited in number and efficacy4,5. The intensity and frequency of occurrence of repetitive behaviors in OCD and ASD can become great enough to displace most other normal behaviors and social interactions in patients with these conditions. In light of the prevalence and debilitating nature of psychiatric conditions characterized by repetitive behaviors, and considering the poor understanding of their causes and limited treatment options, the use of animal models to study these behaviors takes on added urgency.
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 published6-14. In general, these established models can be classified as genetic, pharmacological, neurodevelopmental and behavioral and most show good face, construct and predictive validity6,7. We have used two behavioral models- marble burying and nestlet shredding- to assess repetitive behaviors in mice genetically depleted of serotonin15,16. These methods have numerous advantages not the least of which are their ease of use, the accuracy with which the behaviors can be scored, the spontaneous exhibition of these behaviors in rodents, and their use in high-throughput screening of genetically modified mice for abnormal behavioral phenotypes. Furthermore, each test is carried out in standard and familiar rodent housing cages containing the same bedding used in subjects&#39; home cages, minimizing the need for habituation of mice to novel testing chambers. Food and/or water restriction are not required to &#34;motivate&#34; mice to perform. The marble burying test takes advantage of the proclivity of mice to dig in natural settings (e.g.&#160;burrows, escape tunnels) and in standard cage bedding, and the nestlet shred test capitalizes on the fact that mice are nesting animals by nature that build nests for protection of themselves and their offspring against environmental conditions (e.g.&#160;sound, light, temperature). Using nonspecialized and commonly available rodent housing materials, the marble burying and nestlet shredding tasks are simple and powerful behavioral assays of repetitive, compulsive-like behaviors in mice.

<table><tbody><tr><td>Glass toy marbles</td><td>local toy store</td><td>N/A</td><td>assorted styles, colors, clear, and opaque</td></tr><tr><td>Nestlets</td><td>Ancare</td><td>NES3600</td><td></td></tr><tr><td>N10 series mouse cage</td><td>Ancare</td><td>N10HT</td><td>standard rodent cage with wire top</td></tr><tr><td>R20 series rat cage</td><td>Ancare</td><td>R20</td><td>standard rodent cage with wire top</td></tr><tr><td>Bed-o&#039;Cobs</td><td>The Andersons</td><td>8B</td><td>standard rodent bulk bedding, 1/8 in</td></tr></tbody></table>

marble burying and nestlet shredding as tests of repetitive, compulsive-like behaviors in mice

Obsessive-compulsive disorder (OCD) and autism spectrum disorders (ASD) are serious and debilitating psychiatric conditions and each constitutes a significant public health concern, particularly in children. Both of these conditions are highlighted by the repeated expression of meaningless behaviors. Individuals with OCD often show checking, frequent hand washing, and counting. Children with ASDs also engage in repetitive tapping, arm or hand flapping, and rocking. These behaviors can vary widely in intensity and frequency of expression. More intense forms of repetitive behaviors can even result in injury (e.g.&#160;excessive grooming, hand washing, and self-stimulation). These behaviors are therefore very disruptive and make normal social discourse difficult. Treatment options for repetitive behaviors in OCD and ASDs are somewhat limited and there is great interest in developing more effective therapies for each condition. Numerous animal models for evaluating compulsive-like behaviors have been developed over the past three decades. Perhaps the animal models with the greatest validity and ease of use are the marble burying test and the nestlet shredding test. Both tests take advantage of the fact that the target behaviors occur spontaneously in mice. In the marble burying test, 20 marbles are arrayed on the surface of clean bedding. The number of marbles buried in a 30 min session is scored by investigators blind to the treatment or status of the subjects. In the nestlet shredding test, a nestlet comprised of pulped cotton fiber is preweighed and placed on top of cage bedding and the amount of the nestlet remaining intact after a 30 min test session is determined. Presently, we describe protocols for and show movie documentation of marble burying and nestlet shredding. Both tests are easily and accurately scored and each is sensitive to small changes in the expression of compulsive-like behaviors that result from genetic manipulations, disease, or head injury.

A primary advantage of the marble burying and nestlet shredding tests is the fact that each depends on natural and spontaneous behaviors of mice that can be quantified after test completion, allowing a single investigator to set up an experiment and then remain outside of the testing room until sessions end. A critical component of the marble burying test is the careful removal of the subject from the cage after testing. Mice typically attempt to avoid capture and, in the process, can dislodge or move marbles that were p...

Watch this Scientific Journal Video about Marble Burying and Nestlet Shredding as Tests of Repetitive, Compulsive-like Behaviors in Mice at JoVE.com

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

Disease, head injury, genetic modifications, and treatment of mice with drugs can have profound effects on behavior. Utilizing well-characterized and validated approaches such as marble burying and nestlet shredding, compulsive-like behaviors can be documented accurately in mice as models of human obsessive-compulsive disorder and autism spectrum disorder.

Obsessive-compulsive disorder (OCD) and autism spectrum disorders (ASD) are serious and debilitating psychiatric conditions and each constitutes a ...

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Research

JoVE Journal

Behavior

28.2K Views.  Wayne State University School of Medicine. Disease, head injury, genetic modifications, and treatment of mice with drugs can have profound effects on behavior. Utilizing well-characterized and validated approaches such as marble burying and nestlet shredding, compulsive-like behaviors can be documented accurately in mice as models of human obsessive-compulsive disorder and autism spectrum disorder.

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

Inchworming: A Novel Motor Stereotypy in the BTBR T+ Itpr3tf/J Mouse Model of Autism

Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental disorder characterized by decreased reciprocal social interaction, abnormal communication, and repetitive behaviors with restricted interest. As diagnosis is based on clinical criteria, any potentially relevant rodent models of this heterogeneous disorder should ideally recapitulate these diverse behavioral traits. The BTBR T+ Itpr3tf/J (BTBR) mouse is an established animal model of ASD, displaying repetitive behaviors such as increased grooming, as well as cognitive inflexibility. With respect to social interaction and interest, the juvenile play test has been employed in multiple rodent models of ASD. Here, we show that when BTBR mice are tested in a juvenile social interaction enclosure containing sawdust bedding, they display a repetitive synchronous digging motion. This repetitive motor behavior, referred to as &#34;inchworming,&#34; was named because of the stereotypic nature of the movements exhibited by the mice while moving horizontally across the floor. Inchworming mice must use their fore- and hind-limbs in synchrony to displace the bedding, performing a minimum of one inward and one outward motion. Although both BTBR and C56BL/6J (B6) mice exhibit this behavior, BTBR mice demonstrate a significantly higher duration and frequency of inchworming and a decreased latency to initiate inchworming when placed in a bedded enclosure. We conclude that this newly described behavior provides a measure of a repetitive motor stereotypy that can be easily measured in animal models of ASD.

Inchworming: A Novel Motor Stereotypy in the BTBR T+ Itpr3tf/J Mouse Model of Autism

Inchworming is a highly repetitive synchronous digging motion displayed by BTBR T+ Itpr3tf/J (BTBR) mice when placed in a testing cage with sufficient sawdust bedding. The procedure is a modification of the juvenile social interaction protocol and is used here to assess repetitive motor stereotypies relevant to Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental disorder characterized by decreased reciprocal social interaction, abnormal ...

Assessing Burrowing, Nest Construction, and Hoarding in Mice

Deterioration in the ability to perform "Activities of daily living" (ADL) is an early sign of Alzheimer's disease (AD). Preclinical behavioural screening of possible treatments for AD currently largely focuses on cognitive testing, which frequently demands expensive equipment and lots of experimenter time. However, human episodic memory (the most severely affected aspect of memory in AD) is different to rodent memory, which seems to be largely non-episodic. Therefore the present ways of screening for new AD treatments for AD in rodents are intrinsically unlikely to succeed. A new approach to preclinical screening would be to characterise the ADL of mice. Fortuitously, several such assays have recently been developed at Oxford, and here the three most sensitive and well-characterised are presented.
Burrowing was first developed in Oxford13. It evolved from a need to develop a mouse hoarding paradigm. Most published rodent hoarding paradigms required a distant food source to be linked to the home cage by a connecting passage. This would involve modifying the home cage as well as making a mouse-proof connecting passage and food source. So it was considered whether it would be possible to put the food source inside the cage. It was found that if a container was placed on the floor it was emptied by the next morning., The food pellets were, however, simply deposited in a heap at the container entrance, rather than placed in a discrete place away from the container, as might be expected if the mice were truly hoarding them. Close inspection showed that the mice were performing digging ("burrowing") movements, not carrying the pellets in their mouths to a selected place as they would if truly hoarding them.6



Food pellets are not an essential substrate for burrowing; mice will empty tubes filled with sand, gravel, even soiled bedding from their own cage. Moreover, they will empty a full tube even if an empty one is placed next to it8.



Several nesting protocols exist in the literature. The present Oxford one simplifies the procedure and has a well-defined scoring system for nest quality5. 



A hoarding paradigm was later developed in which the mice, rather than hoarding back to the real home cage, were adapted to living in the "home base" of a hoarding apparatus. This home base was connected to a tube made of wire mesh, the distal end of which contained the food source. This arrangement proved to yield good hoarding behaviour, as long as the mice were adapted to living in the "home base" during the day and only allowed to enter the hoarding tube at night.

Burrowing, nesting, and hoarding are species-typical activities that mice readily perform in the laboratory. This article describes how they can be easily and cheaply assessed. These protocols are extremely sensitive to mouse strain, brain lesions and diseases. Moreover they constitute &#x201C;environmental enrichment&#x201D; for the mice, and embody the &#x201C;Refinement&#x201D; aspect of the &#x201C;3 Rs&#x201D;18.

Deterioration in the ability to perform "Activities of daily living" (ADL) is an early sign of Alzheimer's disease (AD). Preclinical behavioural screening ...

Neuroscience

Novel Object Exploration as a Potential Assay for Higher Order Repetitive Behaviors in Mice

Restricted, repetitive behaviors (RRBs) are a core feature of autism spectrum disorder (ASD) and disrupt the lives of affected individuals. RRBs are commonly split into lower-order and higher-order components, with lower order RRBs consisting of motor stereotypies and higher order RRBs consisting of perseverative and sequencing behaviors. Higher order RRBs are challenging to model in mice. Current assays for RRBs in mice focus primarily on the lower order components, making basic biomedical research into potential treatments or interventions for higher-order RRBs difficult. Here we describe a new assay, novel object exploration. This assay uses a basic open-field arena with four novel objects placed around the perimeter. The test mouse is allowed to freely explore the arena and the order in which the mouse investigates the novel objects is recorded. From these data, patterned sequences of exploration can be identified, as can the most preferred object for each mouse. The representative data shared here and past results using the novel object exploration assay illustrate that inbred mouse strains do demonstrate different behavior in this assay and that strains with elevated lower order RRBs also show elevated patterned behavior. As such, the novel object exploration assay appears to possess good face validity for higher order RRBs in humans and may be a valuable assay for future studies investigating novel therapeutics for ASD.

Higher order restricted, repetitive behaviors (RRBs) disrupt the lives of affected individuals. These behaviors are challenging to model in rodents, making basic biomedical research into potential treatments or interventions for RRBs difficult. Here we describe novel object exploration as a potential assay for higher order RRBs in mice.

Restricted, repetitive behaviors (RRBs) are a core feature of autism spectrum disorder (ASD) and disrupt the lives of affected individuals.  RRBs are ...

Systematic Assessment of Well-Being in Mice for Procedures Using General Anesthesia

In keeping with the 3R Principle (Replacement, Reduction, Refinement) developed by Russel and Burch, scientific research should use alternatives to animal experimentation whenever possible. When there is no alternative to animal experimentation, the total number of laboratory animals used should be the minimum needed to obtain valuable data. Moreover, appropriate refinement measures should be applied to minimize pain, suffering, and distress accompanying the experimental procedure. The categories used to classify the degree of pain, suffering, and distress are non-recovery, mild, moderate, or severe (EU Directive 2010/63). To determine which categories apply in individual cases, it is crucial to use scientifically sound tools.
The well-being-assessment protocol presented here is designed for procedures during which general anesthesia is used. The protocol focuses on home cage activity, the Mouse Grimace Scale, and luxury behaviors such as burrowing and nest building behavior as indicators of well-being. It also uses the free exploratory paradigm for trait anxiety-related behavior. Fecal corticosterone metabolites as indicators of acute stress are measured over the 24-h post-anesthetic period.
The protocol provides scientifically solid information on the well-being of mice following general anesthesia. Due to its simplicity, the protocol can easily be adapted and integrated in a planned study. Although it does not provide a scale to classify distress in categories according to the EU Directive 2010/63, it can help researchers estimate the degree of severity of a procedure using scientifically sound data. It provides a way to improve the assessment of well-being in a scientific, animal-centered manner.

We developed a protocol to assess well-being in mice during procedures using general anesthesia. A series of behavioral parameters indicating levels of well-being as well as glucocorticoid metabolites were analyzed. The protocol can serve as a general aid to estimate the degree of severity in a scientific, animal-centered manner.

In keeping with the 3R Principle (Replacement, Reduction, Refinement) developed by Russel and Burch, scientific research should use alternatives to animal ...

A Behavioral Test Battery for the Repeated Assessment of Motor Skills, Mood, and Cognition in Mice

Pharmacological and toxicological studies in neurodegeneration require comprehensive behavioral analysis in mice because motor dysfunctions and dysfunctions in mood and cognition are common and often shared symptoms in neurodegenerative diseases. Shown here is a behavioral test battery for motor, mood, and cognition, which can be repeatedly tested in a longitudinal study. This battery assesses the overall behavioral phenotype in mice by examining each domain of behavior with at least two independent well-accepted tests (i.e., open-field test and rotarod test for motor function, social interaction test, elevated plus maze test, and forced swim test for emotional function, and Morris water maze test and novel object recognition test for cognitive function). Therefore, this sensitive and comprehensive test battery is a powerful tool for the study of behavioral alternation in neurodegeneration.

A comprehensive behavioral test battery of motor skills, mood&#8212;including social interaction, depression, and anxiety&#8212;and cognition is designed for the repeated assessment of neurodegeneration-related behavioral changes in mice.

Pharmacological and toxicological studies in neurodegeneration require comprehensive behavioral analysis in mice because motor dysfunctions and ...

A Low-Cost, Odor-Reward Association Task for Tests of Learning and Memory

Robust and simple behavioral paradigms of appetitive, associative memory are crucial for researchers interested in cellular and molecular mechanisms of memory. In this paper, an effective and low-cost mouse behavioral protocol is described for examining the effects of physiological manipulation (such as the infusion of pharmacological agents) on the learning rate and duration of odor-reward memory. Representative results are provided from a study examining the differential role of tyrosine kinase receptor activity in short-term (STM) and long-term memory (LTM). Male mice were conditioned to associate a reward (sugar pellet) with one of the two odors, and their memory for the association was tested 2 or 48 h later. Immediately prior to the training, a tyrosine kinase (Trk) receptor inhibitor or vehicle infusions were delivered into the olfactory bulb (OB). Although there was no effect of the infusion on the learning rate, blockade of the Trk receptors in the OB selectively impaired LTM (48 h), and not short-term memory (STM; 2 h). The LTM impairment was attributed to the diminished odor selectivity as measured by the length of the digging time. The culmination of the results of this experiment showed that Trk receptor activation in the OB is the key in olfactory memory consolidation.

An odor-reward, associative learning task was used to investigate the differential effects of physiological manipulation on long-term and short-term memory.

Robust and simple behavioral paradigms of appetitive, associative memory are crucial for researchers interested in cellular and molecular mechanisms of ...

Nest Building Behavior as an Early Indicator of Behavioral Deficits in Mice

Nest building is an innate behavior in male and female rodents, even when raised in laboratory settings. As such, many researchers provide rodents synthetic and/or natural materials (such as twine, tissue, cotton, paper, and hay) as a gauge of their overall well-being and as an ancillary assessment to predict the possible decline in cognition. Typically, changes in nesting behaviors, such as failure to create a nest, indicate a change in health or welfare. In addition, nesting behavior is sensitive to many environmental and physiological challenges, as well as many genetic mutations underlying pathological disease states. The following protocol describes a nesting behavior paradigm that explores the usage of four types of nesting material. In addition, the protocol utilizes intraclass correlations to demonstrate that inter-rater reliability is higher when nests are constructed out of shredded paper compared to other common nesting materials such as cotton squares, paper twists, and soft cob bedding. The chosen methodology and statistical considerations (i.e., intraclass correlation) for this assay may be of interest for those conducting experiments assessing the quality of living of mice.&#160;

Here, we present a protocol to quantify nest building behavior in mice, which is known to be impaired in several neurological disorders and diseases. This protocol examines the utility of four materials and offers the opportunity to quantify the rater agreement in scoring, improving the validity and reliability of the assay.

Nest building is an innate behavior in male and female rodents, even when raised in laboratory settings. As such, many researchers provide rodents ...

A Chronic Sleep Fragmentation Model using Vibrating Orbital Rotor to Induce Cognitive Deficit and Anxiety-Like Behavior in Young Wild-Type Mice

Sleep disturbance is generally common in populations as a chronic disease or a complained event. Chronic sleep disturbance is proposed to be closely linked to the pathogenesis of diseases, especially neurodegenerative diseases. We recently found that 2 months of sleep fragmentation initiated Alzheimer&#8217;s disease (AD)-like behavioral and pathological changes in young wild-type mice. Herein, we present a standardized protocol to achieve chronic sleep fragmentation (CSF). Briefly, CSF was induced by an orbital rotor vibrating at 110 rpm and operating with a repetitive cycle of 10 s-on, 110 s-off, during light-ON phase (8:00 AM&#8211;8:00 PM) continuously for up to 2 months. Impairments of spatial learning and memory, anxiety-like but not depression-like behavior in mice as consequences of CSF modeling, were evaluated with Morris water maze (MWM), Novel object recognition (NOR), Open field test (OFT) and Forced swimming test (FST). In comparison with other sleep manipulations, this protocol minimizes the handling labors and maximizes the modeling efficiency. It produces stable phenotypes in young wild-type mice and can be potentially generated for a variety of research purposes.

Presented here is a protocol for chronic sleep fragmentation (CSF) model achieved by an electrically controlled orbital rotor, which could induce confirmed cognitive deficit and anxiety-like behavior in young wild-type mice. This model can be applied to explore the pathogenesis of chronic sleep disturbance and related disorders.

Sleep disturbance is generally common in populations as a chronic disease or a complained event. Chronic sleep disturbance is proposed to be closely ...

Validating a Murine Model of Angelman Syndrome Using Behavioral Tests

Behavioral Characterization of an Angelman Syndrome Mouse Model

This manuscript describes a battery of behavioral tests available to characterize Angelman syndrome (AS)-like phenotypes in an established murine model of AS. We use the rotarod learning paradigm, detailed gait analysis, and nest building test to detect and characterize animal motor impairments. We test animal emotionality in the open field and elevated plus maze tests, as well as the affect in the tail suspension test. When AS mice are tested in the open field test, the results should be interpreted with care, since motor dysfunctions influence mouse behavior in the maze and alter activity scores.
The reproducibility and effectiveness of the presented behavioral tests has already been validated in several independent Uba3a mouse lines with different knockout variants, establishing this set of tests as an excellent validation tool in AS research. Models with the relevant construct and face validity will warrant further investigations to elucidate the pathophysiology of the disease and grant the development of causal treatments.

Author Spotlight: A Battery of Highly Reproducible Behavioral Tests to Validate an Angelman Syndrome Murine Model 

This manuscript presents a set of highly reproducible behavioral tests to validate an Angelman syndrome mouse model.

This manuscript describes a battery of behavioral tests available to characterize Angelman syndrome (AS)-like phenotypes in an established murine model of ...

Behavioral Assays for Autism Spectrum Disorder in Mouse Models

Strategies for Assessing Autistic-Like Behaviors in Mice

Autism spectrum disorder (ASD) is a neurobiologically complex condition with a heterogeneous genetic etiology. Clinically, ASD is diagnosed by social communication impairments and restrictive or repetitive behaviors, such as hand flapping or lining up objects. These behavioral patterns can be reliably observed in mouse models with ASD-linked genetic mutations, making them highly useful tools for studying the underlying cellular and molecular mechanisms in ASD. Understanding how genetic changes affect the neurobiology and behaviors observed in ASD will facilitate the development of novel targeted therapeutic compounds to ameliorate core behavioral impairments. Our lab has employed several protocols encompassing well-described training and testing procedures that reflect a wide range of behavioral deficits related to ASD. Here, we detail two assays to study the core features of ASD in mouse models: self-grooming (a measure of repetitive behavior) and the three-chamber social interaction test (a measure of social interaction approach and preference for social novelty).

Rodent models are valuable tools for studying core behaviors related to autism spectrum disorder (ASD). In this article, we expound on two behavioral tests for modeling the core features of ASD in mice: self-grooming, which assesses repetitive behavior, and the three-chamber social interaction test, which documents social impairments.

Autism spectrum disorder (ASD) is a neurobiologically complex condition with a heterogeneous genetic etiology. Clinically, ASD is diagnosed by social ...