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Article

Behavioural Characterisation of Macrod1 and Macrod2 Knockout Mice

1
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
2
Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK
3
MRC Harwell Institute, Harwell Campus, Didcot OX11 0RD, UK
*
Author to whom correspondence should be addressed.
Academic Editors: Herwig Schüler and Giovanna Grimaldi
Cells 2021, 10(2), 368; https://doi.org/10.3390/cells10020368
Received: 6 January 2021 / Revised: 3 February 2021 / Accepted: 4 February 2021 / Published: 10 February 2021
(This article belongs to the Special Issue Protein Mono-ADP-Ribosylation in the Control of Cell Functions)
Adenosine diphosphate ribosylation (ADP-ribosylation; ADPr), the addition of ADP-ribose moieties onto proteins and nucleic acids, is a highly conserved modification involved in a wide range of cellular functions, from viral defence, DNA damage response (DDR), metabolism, carcinogenesis and neurobiology. Here we study MACROD1 and MACROD2 (mono-ADP-ribosylhydrolases 1 and 2), two of the least well-understood ADPr-mono-hydrolases. MACROD1 has been reported to be largely localized to the mitochondria, while the MACROD2 genomic locus has been associated with various neurological conditions such as autism, attention deficit hyperactivity disorder (ADHD) and schizophrenia; yet the potential significance of disrupting these proteins in the context of mammalian behaviour is unknown. Therefore, here we analysed both Macrod1 and Macrod2 gene knockout (KO) mouse models in a battery of well-defined, spontaneous behavioural testing paradigms. Loss of Macrod1 resulted in a female-specific motor-coordination defect, whereas Macrod2 disruption was associated with hyperactivity that became more pronounced with age, in combination with a bradykinesia-like gait. These data reveal new insights into the importance of ADPr-mono-hydrolases in aspects of behaviour associated with both mitochondrial and neuropsychiatric disorders. View Full-Text
Keywords: ADP-ribosylation (ADPr); MARylation hydrolases: Macrod1; Macrod2; behaviour; motor-coordination; gait; hyperactivity ADP-ribosylation (ADPr); MARylation hydrolases: Macrod1; Macrod2; behaviour; motor-coordination; gait; hyperactivity
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MDPI and ACS Style

Crawford, K.; Oliver, P.L.; Agnew, T.; Hunn, B.H.M.; Ahel, I. Behavioural Characterisation of Macrod1 and Macrod2 Knockout Mice. Cells 2021, 10, 368. https://doi.org/10.3390/cells10020368

AMA Style

Crawford K, Oliver PL, Agnew T, Hunn BHM, Ahel I. Behavioural Characterisation of Macrod1 and Macrod2 Knockout Mice. Cells. 2021; 10(2):368. https://doi.org/10.3390/cells10020368

Chicago/Turabian Style

Crawford, Kerryanne, Peter L. Oliver, Thomas Agnew, Benjamin H.M. Hunn, and Ivan Ahel. 2021. "Behavioural Characterisation of Macrod1 and Macrod2 Knockout Mice" Cells 10, no. 2: 368. https://doi.org/10.3390/cells10020368

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