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

S Hosie; M Ellis; M Swaminathan; F Ramalhosa; GO Seger; GK Balasuriya; C Gillberg; M Råstam; L Churilov; SJ McKeown; N Yalcinkaya; P Urvil; T Savidge; CA Bell; O Bodin; J Wood; AE Franks; JC Bornstein; EL Hill-Yardin

Journal article

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

S Hosie, M Ellis, M Swaminathan, F Ramalhosa, GO Seger, GK Balasuriya, C Gillberg, M Råstam, L Churilov, SJ McKeown, N Yalcinkaya, P Urvil, T Savidge, CA Bell, O Bodin, J Wood, AE Franks, JC Bornstein, EL Hill-Yardin

Autism Research | WILEY | Published : 2019

DOI: 10.1002/aur.2127

Download PDF

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 dysfuncti..

View full abstract

University of Melbourne Researchers

Suzanne Hosie Author

Leonid Churilov Author

Joel Bornstein Author

Elisa Hill Author

Related Projects (4)

How nutrients and other gut contents produce the gut movements essential to the digestion of food and excretion of waste

This project will identify the mechanisms that control the mixing of food with digestive juices, the absoprtion of nutrients from the gut to..

Altered gastrointestinal function in the neuroligin-3 mouse model of autism

PUBLIC ABSTRACT Disorders in gut function, notably chronic constipation, are a major issue for autistic patients and their families, affect..

Altered gastrointestinal function in the neuroligin-3 mouse model of autism

PUBLIC ABSTRACT Disorders in gut function, notably chronic constipation, are a major issue for autistic patients and their families, affect..

Pathogenesis and therapeutic modulation of aggressive behaviour in a mouse model of autism spectrum disorder

This project focuses on understanding the causes of aggressive behaviour in mice that have a human gene mutation found in autism. Aggressive..

Grants

Awarded by Mayo Clinic

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.