LO RE, Oriana, Tommaso MAZZA and Manlio VINCIGUERRA. Mono-ADP-Ribosylhydrolase MACROD2 Is Dispensable for Murine Responses to Metabolic and Genotoxic Insults. FRONTIERS IN GENETICS. LAUSANNE: FRONTIERS MEDIA SA, 2018, vol. 9, No 654, p. 1-9. ISSN 1664-8021. Available from: https://dx.doi.org/10.3389/fgene.2018.00654.
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Basic information
Original name Mono-ADP-Ribosylhydrolase MACROD2 Is Dispensable for Murine Responses to Metabolic and Genotoxic Insults
Authors LO RE, Oriana (380 Italy, belonging to the institution), Tommaso MAZZA (380 Italy) and Manlio VINCIGUERRA (826 United Kingdom of Great Britain and Northern Ireland, guarantor).
Edition FRONTIERS IN GENETICS, LAUSANNE, FRONTIERS MEDIA SA, 2018, 1664-8021.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10603 Genetics and heredity
Country of publisher Switzerland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 3.517
RIV identification code RIV/00216224:14110/18:00105803
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.3389/fgene.2018.00654
UT WoS 000453107700001
Keywords in English metabolic stress; obesity; MACROD2; irradiation; genotoxic stress response; knock out mouse model
Tags 14110513, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Michal Petr, učo 65024. Changed: 23/4/2024 10:08.
Abstract
ADP-ribosylation is an important post-translational protein modification that regulates diverse biological processes, controlled by dedicated transferases, and hydrolases. Disruption in the gene encoding for MACROD2, a mono-ADP-ribosylhydrolase, has been associated to the Kabuki syndrome, a pediatric congenital disorder characterized by facial anomalies, and mental retardation. Non-coding and structural mutations/variations in MACROD2 have been associated to psychiatric disorders, to obesity, and to cancer. Mechanistically, it has been recently shown that frequent deletions of the MACROD2 alter DNA repair and sensitivity to DNA damage, resulting in chromosome instability, and colorectal tumorigenesis. Whether MACROD2 deletion sensitizes the organism to metabolic and tumorigenic stressors, in absence of other genetic drivers, is unclear. As MACROD2 is ubiquitously expressed in mice, here we generated constitutively whole-body knock-out mice for MACROD2, starting from mouse embryonic stem (ES) cells deleted for the gene using the VelociGeneo (R) technology, belonging to the Knockout Mouse Project (KOMP) repository, a NIH initiative. MACROD2 knock-out mice were viable and healthy, indistinguishable from wild type littermates. High-fat diet administration induced obesity, and glucose/insulin intolerance in mice independent of MACROD2 gene deletion. Moreover, sub-lethal irradiation did not indicate a survival or lethality bias in MACROD2 knock-out mice compared to wild type littermates. Altogether, our data point against a sufficient role of MACROD2 deletion in aggravating high-fat induced obesity and DNA damage-associated lethality, in absence of other genetic drivers.
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