{"doi":"10.1101/2023.02.07.527494","title":"<i>ADP-ribose-acceptor hydrolase 2</i> ( <i>Arh2</i> ) deficiency results in cardiac dysfunction, tumorigenesis, inflammation, and decreased survival","abstract":"Abstract ADP-ribosylation is a reversible reaction with ADP-ribosyltransferases catalyzing the forward reaction and ADP-ribose-acceptor hydrolases (ARHs) hydrolyzing the ADP-ribose acceptor bond. ARH2 is a member of the 39-kDa ARH family (ARH1-3), which is expressed in heart and skeletal muscle. ARH2 failed to exhibit any in vitro enzymatic activity. To determine its possible in vivo activities, Arh2 -knockout (KO) and - heterozygous (Het) mice were generated using CRISPR-Cas9. Arh2 -KO mice exhibited decreased cardiac contractility by MRI, echocardiography and dobutamine stress with cardiomegaly and abnormal motor function. Arh2 -Het mice showed results similar to those seen in Arh2 -KO mice except for cardiomegaly. Arh2 -KO and -Het mice and mouse embryonic fibroblasts (MEFs) developed spontaneous tumors and subcutaneous tumors in nude mice. We identified 13 mutations in Arh2 -Het MEFs and heterozygous tumors, corresponding to human ARH2 mutations in cancers obtained from COSMIC. Of interest, the L116R mutation in Arh2 gene plays a critical role in aggressive tumorigenesis in nude mice, corresponding to human ARH2 mutations in stomach adenocarcinoma. Both genders of Arh2 -KO and -Het mice showed increased unexpectedly deaths and decreased survival rate during a 24-month observation, caused by tumor, inflammation, non-inflammation (e.g., cardiomegaly, dental dysplasia), and congenital diseases. Thus, Arh2 plays a pivotal role in cardiac function, tumorigenesis, inflammation, and overall survival.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":398406,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":925153,"name":"Sachiko Yamashita","orcid":null,"position":1,"is_corresponding":false},{"id":431635,"name":"Hiroko Ishiwata-Endo","orcid":"0000-0002-9962-8206","position":2,"is_corresponding":false},{"id":1174859,"name":"Shunya Oka","orcid":null,"position":3,"is_corresponding":false},{"id":265814,"name":"Zu‐Xi Yu","orcid":"0000-0003-1141-4551","position":4,"is_corresponding":false},{"id":242699,"name":"Chengyu Liu","orcid":"0000-0002-5136-9225","position":5,"is_corresponding":false},{"id":299704,"name":"Danielle Springer","orcid":"0000-0002-6261-9744","position":6,"is_corresponding":false},{"id":321936,"name":"Audrey Noguchi","orcid":null,"position":7,"is_corresponding":false},{"id":1117866,"name":"Morteza Peiravi","orcid":null,"position":8,"is_corresponding":false},{"id":248808,"name":"Victoria Hoffmann","orcid":null,"position":9,"is_corresponding":false},{"id":788237,"name":"Martin J. Lizak","orcid":null,"position":10,"is_corresponding":false},{"id":1174629,"name":"Matthew Medearis","orcid":"0009-0008-5890-3188","position":11,"is_corresponding":false},{"id":484857,"name":"In‐Kwon Kim","orcid":"0000-0002-2779-9735","position":12,"is_corresponding":false},{"id":241249,"name":"Joel Moss","orcid":"0000-0003-1788-1927","position":13,"is_corresponding":false},{"id":241248,"name":"Jiro Kato","orcid":"0000-0003-0318-1794","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:19:47.744358Z","pmid":"36798189","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}