Behavioural Characterisation of <i>Macrod1</i> and <i>Macrod2</i> Knockout Mice

• Main Authors: Kerryanne Crawford, Peter L. Oliver, Thomas Agnew, Benjamin H. M. Hunn, Ivan Ahel
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: Cells
• Subjects: ADP-ribosylation (ADPr); MARylation hydrolases: Macrod1; Macrod2; behaviour; motor-coordination; gait
• Online Access: https://www.mdpi.com/2073-4409/10/2/368

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 <i>MACROD2</i> 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 <i>Macrod1</i> and <i>Macrod2</i> gene knockout (KO) mouse models in a battery of well-defined, spontaneous behavioural testing paradigms. Loss of <i>Macrod1</i> resulted in a female-specific motor-coordination defect, whereas <i>Macrod2</i> 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.