Antioxidant Behavioural Phenotype in the Immp2l Gene Knock-Out Mouse

Lawther, Adam J. and Zieba, Jerzy and Fang, Zhiming and Furlong, Teri M. and Conn, Illya and Govindaraju, Hemna and Choong, Laura L. Y. and Turner, Nigel and Siddiqui, Khawar Sohail and Bridge, Wallace and Merlin, Sam and Hyams, Tzipi Cohen and Killingsworth, Murray and Eapen, Valsamma and Clarke, Raymond A. and Walker, Adam K. (2023) Antioxidant Behavioural Phenotype in the Immp2l Gene Knock-Out Mouse. Genes, 14 (9). p. 1717. ISSN 2073-4425

Full text not available from this repository.
Link to published document: http://doi.org/10.3390/genes14091717

Abstract

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's association with behaviour, we developed the Immp2l(KD) knockout (KO) mouse model which is devoid of Immp2l peptidase activity. Immp2l(KD) -/- KO mice do not display any of the core behavioural symptoms of ASD, albeit homozygous Immp2l(KD) -/- 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 Immp2l(KD) -/- KO mice. To our surprise, we observed that ROS levels were not increased but significantly lowered in our new Immp2l(KD) -/- 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 Immp2l(KD) -/- 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.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 01 May 2024 04:49
Last Modified: 01 May 2024 04:49
URI: http://eprints.victorchang.edu.au/id/eprint/1470

Actions (login required)

View Item View Item