| Project/Area Number |
17590979
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
SHIMIZU Ritsuko University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor, 大学院人間総合科学研究科, 講師 (40226262)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
|
|---|
| Keywords | GATA-1 / GATA-2 / Conditional knockout / Erythrocyte / Megakaryocyte / Hematopoietic stem cell / Proliferation and differentiation / 造血肝細胞 |
|---|
| Research Abstract |
Firstly, we established GATA-1 conditional knockout mice (G1-CK0) and mated with Mx1-Cre mice to generate G1-CKO::Mx1-Cre. In these mice, the GATA-1 hematopoietic cell specific first exon (IE exon) could be effectively deleted in hematopoietic cells by using injected polyinosinic-polycytidylic acid (pIpC) to induce expression of Cre recombinase. One month after pIpC injection, G1-CKO::Mx1-Cre mice developed severe anemia and thrombocytopenia. Immunophenotypical examination revealed that c-Kit^-CD71^+Ter119^<low> immature erythroid progenitors and GATA-1 deficient megakaryocytes were accumulated in bone marrows and spleens.
Secondary, We established and GATA-2 conditional knockout mice (G2-CKO) in which GATA-2 cDNA sandwiched between two loxP sequences was inserted into the translation initiation site of Oata2 gene. To investigate the function of GATA-2 on the hematopoietic cell proliferation in vivo, we established compound mice with Mx1-Cre (G2-CK0::Mx1-Cre) The number of Lin^-c-Kit^+Sca1^+ hematopoietic stem cells for the G2-CKO::Mx1-Cre mice significantly declined compared with those for the control mice after pIpC injection. These findings indicate that the maintenance of hematopoietic stem cells by GATA-2 and the regulation of erythroid/megakaryocytic cell development by GATA-1 are important for adult hematopoiesis.
|
