Mouse Model Systems of Autism Spectrum Disorder: Replicability and Informatics Signature

Kabitzke, P. A.; Morales, D.; He, D.; Cox, K.; Sutphen, J.; Thiede, L.; Sabath, E.; Hanania, T.; Biemans, B.; Brunner, D.

doi:10.1101/561233

Home/Archive/bioRxiv

bioRxiv · 10.1101/561233

Mouse Model Systems of Autism Spectrum Disorder: Replicability and Informatics Signature

Kabitzke, P. A.·Morales, D.·He, D.·Cox, K.·Sutphen, J.·Thiede, L.·Sabath, E.·Hanania, T.·Biemans, B.·Brunner, D.

View original source ↗Export metadata ↓

Abstract

3.BackgroundPhenotyping mouse model systems of human disease has proven to be a difficult task, with frequent poor inter- and intra-laboratory replicability and translatability, particularly in behavioral domains such as social and verbal function. However, establishing robust animal model systems with strong construct validity is of fundamental importance as they are central tools for understanding disease pathophysiology and developing therapeutics. To complete our studies of mouse model systems relevant to autism spectrum disorder (ASD), we present a replication of the main findings from our two published studies comprising five genetic mouse model systems of ASD. MethodsTo assess the robustness of our previous results, we chose the two model systems that showed the greatest phenotypic differences, the Shank3/F and Cntnap2, and repeated assessments of general health, activity, and social behavior. We additionally explored all five model systems in the same framework, comparing all results obtained in this three-yearlong effort using informatics techniques to look for commonalities and differences. ResultsResults in the current study were very similar to our previously published results. The informatics signatures of the two model systems chosen for the replication showed that they were most distinguished by activity levels. Although the two model systems were opposite in this regard, those aspects of their social behavior not confounded by activity (vocalizations) were similar. ConclusionsOur results showed high intra-laboratory replicability of results, even for those with effect sizes that were not particularly large, suggesting that discrepancies in the literature may be dependent on subtle differences in testing conditions, housing enrichment, or background strains and not so much on the variability of the behavioral phenotypes. The overall informatics analysis suggests two main classes of model systems that in some aspects lie on opposite ends of the behavioral spectrum, supporting the view that autism is not a unitary concept.

Source connections

Published article ↗

Explore related subjects

animal behavior and cognition Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Kabitzke, P. A., Morales, D., He, D., Cox, K., Sutphen, J., Thiede, L., Sabath, E., Hanania, T., Biemans, B., Brunner, D.. 2019-02-27. Mouse Model Systems of Autism Spectrum Disorder: Replicability and Informatics Signature. https://doi.org/10.1101/561233

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Can a Tiny Brain Plan? Reconstructing a Predatory Detour inthe Jumping Spider Portia labiata

Planning is the process of evaluating alternative futures to predict outcomes and guide action. Evidence for this process exists in several vertebrates, but remains contested in in-vertebrates. Jumping spiders in the genus Portia show planning-like behavior in lab studies, but how this translates to the wild is unclear, where hunts of potentially lethal spider prey occur over durations of more than an hour in dense foliage. We present the first fully video-recorded wild hunt of any Portia species, with a 3D reconstruction of its forty-two minute long route to attack an orb-weaving spider. The reconstruction suggests P. labiata may have planned its approach, avoiding a route half as long but potentially more conspicuous to the prey's sensory systems.

animal behavior and cognition↗

bioRxiv2026

Assessing Enclosure Modifications to Enhance Accessibility for Zoo-Housed Meerkats (Suricata suricatta)

Scientific advancements have contributed to increased longevity of animals in zoos and aquariums, creating a growing need for environments that remain accessible to geriatric animals and animals with disabilities. However, few empirical studies have evaluated whether accessibility-focused enclosure modifications impact species-appropriate behavior. We evaluated the effects of accessibility modifications on a group of four adult zoo-housed meerkats (Suricata suricatta), including one individual with a forelimb amputation and one geriatric individual. Low-level logs and steps were added to the enclosure to provide intermediate heights and facilitate access to elevated areas. Following the introduction of these enclosure modifications, sentry behavior increased, with all individuals engaging in this behavior compared with only one individual during baseline. The meerkats also increased their overall use of low-elevated areas following modification, although individual responses varied. Posture differed between study phases, with meerkats more frequently adopting tri/quadrupedal postures following modification. Together, these findings suggest that relatively simple accessibility-focused modifications can expand opportunities for geriatric animals and animals with disabilities to engage in species-appropriate behavior. More broadly, this case study highlights the importance of empirically evaluating accessibility interventions and incorporating universal design principles into animal spaces to accommodate individuals with diverse physical abilities and promote positive animal welfare.

animal behavior and cognition↗

bioRxiv2026

Moving Heads, Moving Sounds: Systematic Errors in Auditory Motion Perception

The movement of moving objects seen during self-motion is incorrectly perceived as a result of errors in parsing the visual motion arising from the retina and from information about the movement of the head and eyes in space1. The perception of motion of auditory targets may be even more challenging as previous research suggests that the auditory system lacks dedicated low-level speed processing mechanisms. This study investigates how the perception of a moving auditory sound source is influenced by concurrent head movements, drawing comparisons with established visual motion perception findings and illusions, such as the Filehne Illusion. Participants were asked to move their heads at a fixed speed, either horizontally (left to right or right to left) or vertically (up to down or down to up), while indicating the perceived direction of a moving sound source by using a joystick. A physical sound source was moved silently at a constant speed in fronto-parallel 2D space using a 3x3x3m cable robot. Results showed that head movements created a perceptual bias of the perceived direction of the moving sound source in the opposite direction to the head movement. Responses were less precise during horizontal than vertical head movement, whereas overall directional accuracy did not differ reliably between movement planes. The magnitude of the directional error also depended on the direction of head movement, consistent with the different cues available for horizontal and vertical localization (binaural vs. spectral cues). These findings suggest that similarly to how visual motion perception is distorted by extraretinal signals and the movement of the eyes, so too is auditory motion perception influenced by movement of the ears, revealing errors in the integration of proprioceptive, vestibular and auditory cues that distort the perceived direction of a moving sound source.

animal behavior and cognition↗