---
title: "CNTNAP2 deletion in mice: transient auditory brainstem changes and lasting startle hyperreactivity"
id: "biorxiv-15-cntnap2-deletion-in-mice-causes-developmentally-transient-alterations-in"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-15-cntnap2-deletion-in-mice-causes-developmentally-transient-alterations-in"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.17.752490v1?rss=1"
published_at: "2026-09-19T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# CNTNAP2 deletion in mice: transient auditory brainstem changes and lasting startle hyperreactivity
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-15-cntnap2-deletion-in-mice-causes-developmentally-transient-alterations-in
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.17.752490v1?rss=1)
- **Published At:** 2026-09-19T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Autism spectrum disorder (ASD) commonly includes **auditory** processing differences and hypersensitivity. These may reflect delayed or altered development of the **auditory brainstem**. - Loss-of-function mutations in **CNTNAP2** are causally linked to ASD and have been associated with auditory deficits in other species. - The preprint reports characterization of auditory processing and sensorimotor reactivity in juvenile and adult Cntnap2 knockout (KO) mice to test whether Cntnap2 deletion affects auditory brainstem function and acoustic startle behavior. - Juvenile Cntnap2 KO mice showed larger auditory brainstem response (ABR) **wave III amplitudes** and narrower **wave IV widths**, findings consistent with transient hyperexcitability in the developing auditory brainstem. - Those ABR abnormalities normalized in adult KO mice, indicating the alterations are developmentally transient in mice. - Acoustic startle testing identified a persistent, **sex-specific** phenotype: male KO mice exhibited exaggerated startle responses that continued into adulthood, whereas prepulse inhibition (PPI) remained generally intact across ages and genotypes. - The data indicate that Cntnap2 deletion produces some auditory brainstem abnormalities similar to those observed in rats but leads to species- and sex-specific outcomes for auditory reactivity in mice. - The authors position the Cntnap2 KO mouse as a complementary model for studying neural mechanisms underlying auditory dysfunction relevant to ASD. - The study is a preprint and has not been peer reviewed; methodological details and quantitative metrics beyond the summary in the abstract are not reported in the provided source.
## Clinical Analysis & Structured Key Points
Cntnap2 deletion in mice causes developmentally transient alterations in auditory processing and persistent startle hyperreactivity | bioRxiv Skip to main content New Results Cntnap2 deletion in mice causes developmentally transient alterations in auditory processing and persistent startle hyperreactivity Nita Chan , Shane S.D.I. Seheult , Abigail Warr , Paul A Faure , Susanne Schmid , View ORCID Profile Katrina Y Choe doi: https://doi.org/10.64898/2026.09.17.752490 Nita Chan 1 McMaster University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Shane S.D.I. Seheult 1 McMaster University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abigail Warr 1 McMaster University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Paul A Faure 1 McMaster University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Susanne Schmid 2 University of Western Ontario Find this author on Google Scholar Find this author on PubMed Search for this author on this site Katrina Y Choe 1 McMaster University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Katrina Y Choe For correspondence: choek{at}mcmaster.ca Abstract Info/History Metrics Preview PDF Abstract Autism spectrum disorder (ASD) is a neurodevelopmental condition often associated with auditory symptoms, including impairments in sound perception and hypersensitivity. These symptoms are thought to be partly due to the delayed development of the auditory brainstem, as evidenced through aberrant auditory brainstem responses (ABRs) and exaggerated startle responses in infants diagnosed with ASD. Loss-of-function mutations in CNTNAP2, a gene implicated in auditory processing and language development, are causally associated with ASD. Accordingly, knocking out Cntnap2 causes auditory brainstem impairments in rats; however, it is unknown if similar disruptions are observed in mice due to a possible conserved role of Cntnap2 in the auditory brainstem. To test this, we characterized the development of auditory processing, reactivity, and sensory filtering in juvenile and adult Cntnap2 knockout (KO) mice. We found that juvenile KO mice exhibited larger ABR wave III amplitudes and smaller wave IV widths, which normalized in adult mice, suggesting the possibility of transient hyperexcitability in the developing auditory brainstem. Additionally, our acoustic startle measurements revealed sex-specific phenotypes in which male KO mice exhibit an exaggerated startle response that persists into adulthood, while prepulse inhibition (PPI) remained generally intact in KO mice at both ages. These results demonstrate that loss of Cntnap2 in mice produces auditory brainstem abnormalities similar to rats, but causes species- and sex-specific effects on auditory reactivity, establishing the mouse model as a complementary animal model for investigating neural mechanisms underlying auditory dysfunction in ASD. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared Canadian Institutes of Health Research , PJT-168866 (S.S.) , PJT-183808 (KYC) Natural Sciences and Engineering Research Council , RGPIN-2025-07258 (P.A.F.) , RGPIN-04472-2018 (S.S.) , RGPIN-2021-03732 (KYC) , Canada Graduate Research Scholarship-Doctoral (SDIS) Canada Research Chairs , CRC-2020-00071 Canada Foundation for Innovation , John Evans Leaders Fund #40750 (KYC) Government of Ontario, https://ror.org/015pzp858 , Research Infrastructure Grant (KYC) , Ontario Graduate Scholarship (NC) Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted September 19, 2026. Download PDF Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. 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Seheult , Abigail Warr , Paul A Faure , Susanne Schmid , Katrina Y Choe bioRxiv 2026.09.17.752490; doi: https://doi.org/10.64898/2026.09.17.752490 Share This Article: Copy Citation Tools Cntnap2 deletion in mice causes developmentally transient alterations in auditory processing and persistent startle hyperreactivity Nita Chan , Shane S.D.I. Seheult , Abigail Warr , Paul A Faure , Susanne Schmid , Katrina Y Choe bioRxiv 2026.09.17.752490; doi: https://doi.org/10.64898/2026.09.17.752490 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Genetics Subject Areas All Articles Animal Behavior and Cognition (8013) Biochemistry (18737) Bioengineering (14888) Bioinformatics (44415) Biophysics (22597) Cancer Biology (19722) Cell Biology (26899) Clinical Trials (138) Developmental Biology (13964) Ecology (21005) Epidemiology (2067) Evolutionary Biology (25454) Genetics (16165) Genomics (23505) Immunology (18703) Microbiology (42483) Molecular Biology (18058) Neuroscience (93440) Paleontology (700) Pathology (2977) Pharmacology and Toxicology (5094) Physiology (8114) Plant Biology (15999) Scientific Communication and Education (2095) Synthetic Biology (4560) Systems Biology (10235) Zoology (2391)
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