| http://purl.uniprot.org/citations/30553776 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30553776 | http://www.w3.org/2000/01/rdf-schema#comment | "SMC3 encodes a subunit of the cohesin complex that has canonical roles in regulating sister chromatids segregation during mitosis and meiosis. Recurrent heterozygous mutations in SMC3 have been reported in acute myeloid leukemia (AML) and other myeloid malignancies. In this study, we investigated whether the missense mutations in SMC3 might have dominant-negative effects or phenocopy loss-of-function effects by comparing the consequences of Smc3-deficient and -haploinsufficient mouse models. We found that homozygous deletion of Smc3 during embryogenesis or in adult mice led to hematopoietic failure, suggesting that SMC3 missense mutations are unlikely to be associated with simple dominant-negative phenotypes. In contrast, haploinsufficiency was tolerated during embryonic and adult hematopoiesis. Under steady-state conditions, Smc3 haploinsufficiency did not alter colony forming in methylcellulose, only modestly decreased mature myeloid cell populations, and led to limited expression changes and chromatin alteration in Lin-cKit+ bone marrow cells. However, following transplantation, engraftment, and subsequent deletion, we observed a hematopoietic competitive disadvantage across myeloid and lymphoid lineages and within the stem/progenitor compartments. This disadvantage was not affected by hematopoietic stresses, but was partially abrogated by concurrent Dnmt3a haploinsufficiency, suggesting that antecedent mutations may be required to optimize the leukemogenic potential of Smc3 mutations."xsd:string |
| http://purl.uniprot.org/citations/30553776 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.exphem.2018.11.008"xsd:string |
| http://purl.uniprot.org/citations/30553776 | http://purl.uniprot.org/core/author | "Wang T."xsd:string |
| http://purl.uniprot.org/citations/30553776 | http://purl.uniprot.org/core/author | "Glover B."xsd:string |
| http://purl.uniprot.org/citations/30553776 | http://purl.uniprot.org/core/author | "Miller C.A."xsd:string |
| http://purl.uniprot.org/citations/30553776 | http://purl.uniprot.org/core/author | "Welch J.S."xsd:string |
| http://purl.uniprot.org/citations/30553776 | http://purl.uniprot.org/core/author | "Hadwiger G."xsd:string |
| http://purl.uniprot.org/citations/30553776 | http://purl.uniprot.org/core/author | "di Martino O."xsd:string |
| http://purl.uniprot.org/citations/30553776 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/30553776 | http://purl.uniprot.org/core/name | "Exp Hematol"xsd:string |
| http://purl.uniprot.org/citations/30553776 | http://purl.uniprot.org/core/pages | "70-84.e6"xsd:string |
| http://purl.uniprot.org/citations/30553776 | http://purl.uniprot.org/core/title | "Smc3 is required for mouse embryonic and adult hematopoiesis."xsd:string |
| http://purl.uniprot.org/citations/30553776 | http://purl.uniprot.org/core/volume | "70"xsd:string |
| http://purl.uniprot.org/citations/30553776 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/30553776 |
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