Basis of hematopoietic defects in platelet-derived growth factor (PDGF)-B and PDGF β-receptor null mice
Basis of hematopoietic defects in platelet-derived growth factor (PDGF)-B and PDGF β-receptor null mice
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DOI：
10.1182/blood.v97.7.1990
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发表时间：
2001-04-01
期刊：
影响因子：
20.3
通讯作者：
Raines, EW
中科院分区：
文献类型：
--
作者：
Kaminski, WE;Lindahl, P;Raines, EW
小鼠的血小板衍生生长因子(PDGF)-B和PDGFβ受体(PDGFRβ)缺乏是胚胎致死的，并导致心血管、肾脏、胎盘和血液系统的疾病。血液学疾病被描述，并显示与肝脏细胞减少的相关性。为了探讨可能的原因，我们评估了胎肝细胞的体外集落形成活性，并通过将突变的胎肝细胞移植到致死性照射的受者体内证明了造血嵌合体的存在。发现突变菌落的形成与野生型对照相当。用PDGFB(-/-)、PDGFRβ(-/-)或野生型胎河细胞重组的造血细胞嵌合体与供者粒细胞、单核细胞、B细胞和T细胞完全植入(大于98%)，并且没有突变体中看到的心血管或血液异常。在小鼠胚胎中，PDGF-B由血管内皮细胞和巨核细胞表达。出生后，在巨噬细胞和神经元中可以看到表达。这项研究表明，造血PDGF-B或PDGFRβ的表达对于造血或心血管系统的完整性并不是必需的。有人认为，由胎盘、心脏或血管中的突变缺陷引起的代谢应激可能会导致肝脏生长受损和血细胞生成减少。这项研究中的嵌合体模型将成为测试PDGF在炎症和免疫反应中的作用的有价值的工具。(血。2001年；97：1990-1998)(C)2001由美国血液病学会主办。
Platelet-derived growth factor (PDGF)-B and PDGF beta -receptor (PDGFR beta) deficiency in mice is embryonic lethal and results in cardiovascular, renal, placental, and hematologic disorders. The hematologic disorders are described, and a correlation with hepatic hypocellularity is demonstrated. To explore possible causes, the colony-forming activity of fetal liver cells in vitro was assessed, and hematopoietic chimeras were demonstrated by the transplantation of mutant fetal liver cells into lethally irradiated recipients. It was found that mutant colony formation is equivalent to that of wild-type controls. Hematopoietic chimeras reconstituted with PDGFB(-/-), PDGFR beta (-/-), or wild-type fetal river cells show complete engraftment (greater than 98%) with donor granulocytes, monocytes, B cells, and T cells and display none of the cardiovascular or hematologic abnormalities seen in mutants. In mouse embryos, PDGF-B is expressed by vascular endothelial cells and megakaryocytes. After birth, expression is seen in macrophages and neurons. This study demonstrates that hematopoietic PDGF-B or PDGFR beta expression is not required for hematopoiesis or integrity of the cardiovascular system. It is argued that metabolic stress arising from mutant defects in the placenta, heart, or blood vessels may lead to impaired liver growth and decreased production of blood cells. The chimera models in this study will serve as valuable tools to test the role of PDGF in inflammatory and immune responses. (Blood. 2001;97:1990-1998) (C) 2001 by The American Society of Hematology.