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Extending this notion to in vivo conditions, we found that the knock-in ES cell clones with AML1 mutants, which retain trans-activation subdomains but lack C-terminal repression subdomains including the conserved VWRPY motif, contribute to hematopoietic tissues in chimera mice. We also found that germline mice homozygous for the mutated AML1 allele, which lacks the VWRPY motif, exhibit a minimal effect on hematopoietic development, as was observed in control knock-in mice with full-length AML1. On the other hand, reduced cell numbers and deviant CD4 expression were observed during early T-lymphoid ontogeny in the VWRPY-deficient mice, whereas the contribution to the thymus by the corresponding ES cell clones was inadequate. These findings demonstrate that AML1 with its trans-activating subdomains is essential and sufficient for hematopoietic development in the context of the entire mouse. In addition, its trans-repression activity, depending on the C-terminal VWRPY motif, plays a role in early thymocyte development.<\/jats:p>","DOI":"10.1182\/blood-2003-06-2109","type":"journal-article","created":{"date-parts":[[2003,9,23]],"date-time":"2003-09-23T01:36:27Z","timestamp":1064280987000},"page":"562-570","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":49,"title":["VWRPY motif\u2013dependent and \u2013independent roles of AML1\/Runx1 transcription factor in murine hematopoietic development"],"prefix":"10.1182","volume":"103","author":[{"given":"Motohiro","family":"Nishimura","sequence":"first","affiliation":[{"name":"From the Departments of Hygiene, Thoracic Surgery, Pediatrics, and Hematology\/Oncology, Kyoto Prefectural University of Medicine, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Fukushima-Nakase","sequence":"additional","affiliation":[{"name":"From the Departments of Hygiene, Thoracic Surgery, Pediatrics, and Hematology\/Oncology, Kyoto Prefectural University of Medicine, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Fujita","sequence":"additional","affiliation":[{"name":"From the Departments of Hygiene, Thoracic Surgery, Pediatrics, and Hematology\/Oncology, Kyoto Prefectural University of Medicine, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsushige","family":"Nakao","sequence":"additional","affiliation":[{"name":"From the Departments of Hygiene, Thoracic Surgery, Pediatrics, and Hematology\/Oncology, Kyoto Prefectural University of Medicine, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Toda","sequence":"additional","affiliation":[{"name":"From the Departments of Hygiene, Thoracic Surgery, Pediatrics, and Hematology\/Oncology, Kyoto Prefectural University of Medicine, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuo","family":"Kitamura","sequence":"additional","affiliation":[{"name":"From the Departments of Hygiene, Thoracic Surgery, Pediatrics, and Hematology\/Oncology, Kyoto Prefectural University of Medicine, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Abe","sequence":"additional","affiliation":[{"name":"From the Departments of Hygiene, Thoracic Surgery, Pediatrics, and Hematology\/Oncology, Kyoto Prefectural University of Medicine, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsukasa","family":"Okuda","sequence":"additional","affiliation":[{"name":"From the Departments of Hygiene, Thoracic Surgery, Pediatrics, and Hematology\/Oncology, Kyoto Prefectural University of Medicine, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021219342950600_REF1","doi-asserted-by":"crossref","unstructured":"Orkin SH. 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