Behavioural Characterisation of Macrod1 and Macrod2 Knockout Mice
Open Access
- 9 February 2021
- Vol. 10 (2), 368
- https://doi.org/10.3390/cells10020368
Abstract
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.Keywords
Funding Information
- Wellcome Trust (210634)
- Cancer Research UK (C35050/A22284)
- Biotechnology and Biological Sciences Research Council (BB/R007195/1)
This publication has 98 references indexed in Scilit:
- Activation of the Aryl Hydrocarbon Receptor Sensitizes Mice to Nonalcoholic Steatohepatitis by Deactivating Mitochondrial Sirtuin Deacetylase Sirt3Molecular and Cellular Biology, 2013
- mdx Mice Manifest More Severe Muscle Dysfunction and Diaphragm Force Deficits than Do mdx MiceThe American Journal of Pathology, 2011
- Identification of Macrodomain Proteins as Novel O-Acetyl-ADP-ribose DeacetylasesJournal of Biological Chemistry, 2011
- LRP16 Integrates into NF-κB Transcriptional Complex and Is Required for Its Functional ActivationPLOS ONE, 2011
- Hotspots of Large Rare Deletions in the Human GenomePLOS ONE, 2010
- Elucidating the genetic architecture of familial schizophrenia using rare copy number variant and linkage scansProceedings of the National Academy of Sciences of the United States of America, 2009
- Locomotion and muscle mass measures in a murine model of collagen-induced arthritisBMC Musculoskeletal Disorders, 2009
- Rods-cones and melanopsin detect light and dark to modulate sleep independent of image formationProceedings of the National Academy of Sciences, 2008
- A dominant mutation in Snap25 causes impaired vesicle trafficking, sensorimotor gating, and ataxia in the blind-drunk mouseProceedings of the National Academy of Sciences, 2007
- Mitochondrial dysfunction and oxidative stress in neurodegenerative diseasesNature, 2006