{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:55:03Z","timestamp":1787316903072,"version":"build-2736575974"},"reference-count":102,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"a Sydney Partnership for Health Education Research and Enterprise (SPHERE)","award":["PF-15-014"],"award-info":[{"award-number":["PF-15-014"]}]},{"name":"National Breast Cancer Foundation Australia","award":["PF-15-014"],"award-info":[{"award-number":["PF-15-014"]}]},{"name":"the Schizophrenia Research Institute, UNSW, Australia","award":["PF-15-014"],"award-info":[{"award-number":["PF-15-014"]}]},{"name":"Neuroscience Research Australia, NSW, Australia","award":["PF-15-014"],"award-info":[{"award-number":["PF-15-014"]}]},{"name":"Australian Government Research Training Program Scholarships","award":["PF-15-014"],"award-info":[{"award-number":["PF-15-014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Mitochondrial dysfunction is strongly associated with autism spectrum disorder (ASD) and the Inner mitochondrial membrane protein 2-like (IMMP2L) gene is linked to autism inheritance. However, the biological basis of this linkage is unknown notwithstanding independent reports of oxidative stress in association with both IMMP2L and ASD. To better understand IMMP2L\u2019s association with behaviour, we developed the Immp2lKD knockout (KO) mouse model which is devoid of Immp2l peptidase activity. Immp2lKD \u2212\/\u2212 KO mice do not display any of the core behavioural symptoms of ASD, albeit homozygous Immp2lKD \u2212\/\u2212 KO mice do display increased auditory stimulus-driven instrumental behaviour and increased amphetamine-induced locomotion. Due to reports of increased ROS and oxidative stress phenotypes in an earlier truncated Immp2l mouse model resulting from an intragenic deletion within Immp2l, we tested whether high doses of the synthetic mitochondrial targeted antioxidant (MitoQ) could reverse or moderate the behavioural changes in Immp2lKD \u2212\/\u2212 KO mice. To our surprise, we observed that ROS levels were not increased but significantly lowered in our new Immp2lKD \u2212\/\u2212 KO mice and that these mice had no oxidative stress-associated phenotypes and were fully fertile with no age-related ataxia or neurodegeneration as ascertained using electron microscopy. Furthermore, the antioxidant MitoQ had no effect on the increased amphetamine-induced locomotion of these mice. Together, these findings indicate that the behavioural changes in Immp2lKD \u2212\/\u2212 KO mice are associated with an antioxidant-like phenotype with lowered and not increased levels of ROS and no oxidative stress-related phenotypes. This suggested that treatments with antioxidants are unlikely to be effective in treating behaviours directly resulting from the loss of Immp2l\/IMMP2L activity, while any behavioural deficits that maybe associated with IMMP2L intragenic deletion-associated truncations have yet to be determined.<\/jats:p>","DOI":"10.3390\/genes14091717","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T08:35:05Z","timestamp":1693298105000},"page":"1717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Antioxidant Behavioural Phenotype in the Immp2l Gene Knock-Out Mouse"],"prefix":"10.3390","volume":"14","author":[{"given":"Adam J.","family":"Lawther","sequence":"first","affiliation":[{"name":"Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick, NSW 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Zieba","sequence":"additional","affiliation":[{"name":"Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick, NSW 2031, Australia"},{"name":"Department of Psychology, University of Rzeszow, 35-310 Rzeszow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Fang","sequence":"additional","affiliation":[{"name":"Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Ingham Institute for Applied Medical Research, Sydney, NSW 2170, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teri M.","family":"Furlong","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Illya","family":"Conn","sequence":"additional","affiliation":[{"name":"Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick, NSW 2031, Australia"},{"name":"Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemna","family":"Govindaraju","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Biomedical Sciences, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L. Y.","family":"Choong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Biomedical Sciences, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0119-9328","authenticated-orcid":false,"given":"Nigel","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Biomedical Sciences, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8574-3177","authenticated-orcid":false,"given":"Khawar Sohail","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wallace","family":"Bridge","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2103-4974","authenticated-orcid":false,"given":"Sam","family":"Merlin","sequence":"additional","affiliation":[{"name":"Medical Science, School of Science, Western Sydney University, Campbelltown, Sydney, NSW 2751, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8777-3054","authenticated-orcid":false,"given":"Tzipi Cohen","family":"Hyams","sequence":"additional","affiliation":[{"name":"Ingham Institute for Applied Medical Research, Sydney, NSW 2170, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6125-1183","authenticated-orcid":false,"given":"Murray","family":"Killingsworth","sequence":"additional","affiliation":[{"name":"Ingham Institute for Applied Medical Research, Sydney, NSW 2170, Australia"},{"name":"NSW Health Pathology, Liverpool Hospital Campus, 1 Campbell Street, Liverpool, NSW 2107, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6296-8306","authenticated-orcid":false,"given":"Valsamma","family":"Eapen","sequence":"additional","affiliation":[{"name":"Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Ingham Institute for Applied Medical Research, Sydney, NSW 2170, Australia"},{"name":"Academic Unit of Infant Child and Adolescent Services (AUCS), South Western Sydney Local Health District, Liverpool, NSW 2170, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7196-9623","authenticated-orcid":false,"given":"Raymond A.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Ingham Institute for Applied Medical Research, Sydney, NSW 2170, Australia"},{"name":"Academic Unit of Infant Child and Adolescent Services (AUCS), South Western Sydney Local Health District, Liverpool, NSW 2170, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3772-5745","authenticated-orcid":false,"given":"Adam K.","family":"Walker","sequence":"additional","affiliation":[{"name":"Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick, NSW 2031, Australia"},{"name":"Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3717215","DOI":"10.1155\/2018\/3717215","article-title":"Oxidative Stress, Maternal Diabetes, and Autism Spectrum Disorders","volume":"2018","author":"Carpita","year":"2018","journal-title":"Oxid. 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