J 2018

Mono-ADP-Ribosylhydrolase MACROD2 Is Dispensable for Murine Responses to Metabolic and Genotoxic Insults

LO RE, Oriana, Tommaso MAZZA a Manlio VINCIGUERRA

Základní údaje

Originální název

Mono-ADP-Ribosylhydrolase MACROD2 Is Dispensable for Murine Responses to Metabolic and Genotoxic Insults

Autoři

LO RE, Oriana (380 Itálie, domácí), Tommaso MAZZA (380 Itálie) a Manlio VINCIGUERRA (826 Velká Británie a Severní Irsko, garant)

Vydání

FRONTIERS IN GENETICS, LAUSANNE, FRONTIERS MEDIA SA, 2018, 1664-8021

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10603 Genetics and heredity

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 3.517

Kód RIV

RIV/00216224:14110/18:00105803

Organizační jednotka

Lékařská fakulta

DOI

UT WoS

000453107700001

Klíčová slova anglicky

metabolic stress; obesity; MACROD2; irradiation; genotoxic stress response; knock out mouse model

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 23. 4. 2024 10:08, Mgr. Michal Petr

Anotace

V originále

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.