The effect of GPI‐anchor deficiency on apoptosis in mice carrying a Piga gene mutation in hematopoietic cells
The effect of GPI‐anchor deficiency on apoptosis in mice carrying a Piga gene mutation in hematopoietic cells
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GPI锚定缺陷对携带Piga基因突变小鼠造血细胞凋亡的影响
DOI：
10.1189/jlb.72.6.1228
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发表时间：
2002
影响因子：
5.5
通讯作者：
M. Bessler
中科院分区：
文献类型：
--
作者：
S. Kulkarni;M. Bessler
糖基磷脂酰肌醇（GPI）锚被多种蛋白质用于连接到细胞表面。阵发性睡眠性血红蛋白尿症患者的部分血细胞缺乏GPI锚定蛋白。这是由获得基因PIGA突变的细胞克隆的扩增引起的，PIGA基因在GPI锚的合成中是必不可少的。允许PIGA−细胞扩增的生长/存活优势的性质尚不清楚。在患者的血细胞中发现了对细胞凋亡的敏感性降低，但PIGA基因突变对这一发现的贡献仍然存在争议。因此，我们研究了造血细胞中含有靶向Piga基因突变的小鼠的细胞凋亡。当暴露于各种凋亡刺激物时，PIGA−胸腺细胞、粒细胞和造血祖细胞中的凋亡与来自同一小鼠或野生型对照的PIGA+细胞中诱导的凋亡相似。同样，全身γ辐射也没有产生PIGA-造血干细胞的体内存活优势。我们的研究结果表明，Piga基因突变不会改变细胞死亡的易感性，这表明除了PIGA基因突变之外，其他因素对促进PIGA−细胞的克隆生长是必要的。
Glycosyl phosphatidylinositol (GPI) anchors are used by a variety of proteins to link to the cell surface. GPI‐anchored proteins are deficient on a proportion of blood cells from patients with paroxysmal nocturnal hemoglobinuria. This is caused by the expansion of a cell clone that has acquired a mutation in a gene, PIGA, which is essential in the synthesis of GPI anchors. The nature of the growth/survival advantage permitting the expansion of PIGA− cells is unknown. A decreased susceptibility to apoptosis has been found in blood cells from patients, but the contribution of the PIGA gene mutation to this finding remained controversial. Therefore, we investigated apoptosis in mice that harbor a targeted Piga gene mutation in hematopoietic cells. When exposed to a variety of apoptotic stimuli, apoptosis in PIGA− thymocytes, granulocytes, and hematopoietic progenitor cells was similar to apoptosis induced in PIGA+ cells from the same mouse or from wild‐type controls. Similarly, whole‐body γ‐irradiation did not produce an in vivo survival advantage of PIGA− hematopoietic stem cells. Our findings imply that a Piga gene mutation does not alter susceptibility to cell death, indicating that other factors in addition to the PIGA gene mutation are necessary to promote the clonal outgrowth of PIGA− cells.
研究方向为阵发性睡眠性血红蛋白尿症。
DOI：
10.1016/s0167-5699(98)01424-8
发表时间：
1999
期刊：
Immunology today
影响因子：
--
作者：
Dunn,DE;Ware,RE;Parker,CJ;Mishoe,HO;Young,NS
通讯作者：
Young,NS
DOI：
10.1073/pnas.94.16.8756
发表时间：
1997-08-05
影响因子：
11.1
作者：
Brodsky, RA;Vala, MS;Jones, RJ
通讯作者：
Jones, RJ