嵌合体(遗传学)
阵发性夜间血红蛋白尿
生物
造血
种系突变
免疫学
克隆(Java方法)
骨髓
干细胞
突变体
体细胞
优势(遗传学)
分子生物学
突变
遗传学
基因
作者
K. Kawagoe,Daisuke Kitamura,Masaru Okabe,Ichiro Taniuchi,Masahito Ikawa,Takeshi Watanabe,Taroh Kinoshita,Junji Takeda
出处
期刊:Blood
[American Society of Hematology]
日期:1996-05-01
卷期号:87 (9): 3600-3606
被引量:236
标识
DOI:10.1182/blood.v87.9.3600.bloodjournal8793600
摘要
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder characterized by complement-mediated hemolysis. Abnormal hematopoietic cells from patients with PNH are deficient in glycosylphosphatidylinositol (GPI)-anchored proteins and clonally dominate various hematopoietic lineages in the bone marrow and the peripheral blood. Analysis of many patients with PNH has showed that somatic mutation in the X-linked gene PIG-A is responsible for the GPI- anchor deficiency in PNH. The PIG-A mutation must also be relevant to the clonal dominance of GPI-anchor deficient (GPI-) blood cells because two or more PIG-A mutant clones become dominant in many patients. However, whether the PIG-A mutation alone is sufficient for clonal dominance is not known. To address this question, we generated chimeric mice using Pig-a (the murine homologue of PIG-A) disrupted embryonic stem (ES) cells, in which the animals are chimeric with respect to the surface expression of GPI-anchored proteins. The chimerism of hematopoietic and nonhematopoietic tissues in such mice was always low, suggesting that the higher contribution of Pig-a disrupted GPI- cells had a lethal effect on the chimera. GPI- cells appeared in the peripheral blood of some of the chimeric mice. However, the percentage of GPI- erythrocytes did not increase for 10 months after birth, implying that the Pig-a mutation alone does not immediately cause the clonal dominance of GPI- blood cells; another pathologic or physiologic change(s) in the hematopoietic environments or in the clone itself may be necessary.
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