Gastrointestinal dysfunction in patients and mice expressing the autism-associated R451C mutation in neuroligin-3

Suzanne Hosie; Melina Ellis; Mathusi Swaminathan; Fatima Ramalhosa; Gracia O Seger; Gayathri K Balasuriya; Christopher Gillberg; Maria Rastam; Leonid Churilov; Sonja J McKeown; Nalzi Yalcinkaya; Petri Urvil; Tor Savidge; Carolyn A Bell; Oonagh Bodin; Jen Wood; Ashley E Franks; Joel C Bornstein; Elisa L Hill-Yardin

Journal article

Gastrointestinal dysfunction in patients and mice expressing the autism-associated R451C mutation in neuroligin-3

Suzanne Hosie, Melina Ellis, Mathusi Swaminathan, Fatima Ramalhosa, Gracia O Seger, Gayathri K Balasuriya, Christopher Gillberg, Maria Rastam, Leonid Churilov, Sonja J McKeown, Nalzi Yalcinkaya, Petri Urvil, Tor Savidge, Carolyn A Bell, Oonagh Bodin, Jen Wood, Ashley E Franks, Joel C Bornstein, Elisa L Hill-Yardin

AUTISM RESEARCH | WILEY | Published : 2019

DOI: 10.1002/aur.2127

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Abstract

Gastrointestinal (GI) problems constitute an important comorbidity in many patients with autism. Multiple mutations in the neuroligin family of synaptic adhesion molecules are implicated in autism, however whether they are expressed and impact GI function via changes in the enteric nervous system is unknown. We report the GI symptoms of two brothers with autism and an R451C mutation in Nlgn3 encoding the synaptic adhesion protein, neuroligin-3. We confirm the presence of an array of synaptic genes in the murine GI tract and investigate the impact of impaired synaptic protein expression in mice carrying the human neuroligin-3 R451C missense mutation (NL3R451C ). Assessing in vivo gut dysfunct..

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University of Melbourne Researchers

Joel Bornstein Author Anatomy and Physiology

Elisa Hill Author Anatomy and Physiology

Leonid Churilov Author Medicine - Royal Melbourne Hospital

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Grants

Awarded by United States Department of Defense's Congressionally Directed Medical Research Programs (CDMRP) Autism Research Program

Awarded by National Health and Medical Research Council (NHMRC)

Awarded by ARC Future Fellowship

Awarded by National Institute of Allergy and Infectious Diseases

Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

Funding Acknowledgements

This work was supported by an Idea Development Award from the United States Department of Defense's Congressionally Directed Medical Research Programs (CDMRP) Autism Research Program (AR110134) to E.L.H.-Y. and J.C.B.; the Victorian Government through the Operational Infrastructure Scheme, National Health and Medical Research Council (NHMRC) project grants (APP566642 to J.C.B. and APP1047674 to E.L.H.-Y.) and the Royal Melbourne Hospital Neuroscience Foundation. E.L.H.-Y. also received an ARC Future Fellowship (FT160100126) and an RMIT Vice Chancellor's Senior Research Fellowship which supported G.K.B. and S.H. T.S., P.U., and N.Y. were funded by grants RO1AI100914, P30-DK56338, and U01-AI24290 awards to Baylor College of Medicine funded from the National Institute of Allergy and Infectious Diseases and National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health (T.C.S.). The Hu antibody was a gift from Dr. V. Lennon, Mayo Clinic, USA. The authors thank Laura Parry for gene expression experimental design, M. Mohsenipour for genotyping, Candice Fung for primer design, Athena Latina for microbial sampling, M. Kesar, B. McInnes, T. Drever, M. Williams, and S. Taverner for animal care and E. Mayer, A. Moulden, and R. Savarirayan for their constructive comments on this manuscript.