2005 Fiscal Year Final Research Report Summary
Molecular analysis for hematopoietic regulation by transcription factor, AML1/Runxl.
| Project/Area Number |
16590955
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kyoto Prefectural University of Medicine Graduate School of Medical Science |
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Principal Investigator |
OKUDA Tsukasa Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Associate Professor, 医学研究科, 助教授 (30291587)
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| Project Period (FY) |
2004 – 2005
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| Keywords | AML1 / Runx1 / runt / CBFA1 / Hematopoiesis / Leukemia / Transcription Factor / Gene-Targeting |
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| Research Abstract |
AML1/Runx1 is a frequent target of human leukemia-associated gene alteration, and it encodes a transcription factor which plays non-redundant biologic roles in initial development of definitive hematopoiesis, T -cell development, and platelet production. AML1/Runx1 and two closely related family genes, AML2/Runx3 and AML3/Runx2/Cbfa1, present in mammals, comprise the Runt-domain transcription factor family. Although they share closely related structural and biochemical properties, gene-targeting experiments have revealed distinct biologic roles. To directly determine if there is functional overlap among Runx family molecules, we replaced the C-terminal portion of AML1 with that derived from each of the family members, which are variable in contrast to conserved Runt domain, using the gene knock-in approach. We found that C-terminal portions of either AML2 or AML3 could functionally replace that of AML1 for myeloid development in culture and within the entire mouse. However, while AML2 substituted for AML1 could effectively rescue lymphoid lineages, AML3 could not, resulting in a smaller thymus and lymphoid deficiency in peripheral blood. Substitution by the C-terminal portion of AML3 also led to high infantile mortality and growth retardation, suggesting that AML1 has as yet unidentified effects on these phenotypes. Thus, the C-terminal portions of Runx family members have both similar and distinct biologic functions.
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