IMPAIRED EXPANSION OF MOUSE B-CELL PROGENITORS LACKING BTK
IMPAIRED EXPANSION OF MOUSE B-CELL PROGENITORS LACKING BTK
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DOI：
10.1016/1074-7613(95)90115-9
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发表时间：
1995-09-01
期刊：
影响因子：
32.4
通讯作者：
PERLMUTTER, RM
中科院分区：
文献类型：
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作者：
KERNER, JD;APPLEBY, MW;PERLMUTTER, RM
编码蛋白酪氨酸激酶Btk的基因突变与人类B细胞免疫缺陷x连锁无球蛋白血症（XLA）有关。在小鼠中，Btk pleckstrin同源结构域的点突变与较轻的x连锁免疫缺陷（rid）分离。为了评估Btk功能在小鼠淋巴细胞生成中的重要性，我们生成了多个携带Btk基因靶向破坏的胚胎干细胞克隆，并检测了它们在C57BL/6和RAG2（-/-）宿主嵌合动物中产生淋巴细胞的潜力。这些小鼠提供了一套补充的体内竞争分析，正式建立了rid表型的遗传基础。虽然null突变产生的表型与rid非常相似，但它也损害了B细胞前体的扩增。我们的研究结果表明，Btk缺乏对小鼠和人类的影响仅在数量上有所不同，并且代表相同的疾病过程。
Mutations in the gene encoding the protein tyrosine kinase Btk are associated with the human B cell immunodeficiency X-linked agammaglobulinemia (XLA). In the mouse, a point mutation in the Btk pleckstrin homology domain segregates with a milder X-linked immunodeficiency (rid). To assess the importance of Btk function in murine lymphopoiesis, we generated multiple embryonic stem cell clones bearing a targeted disruption of the btk gene and examined their potential to produce lymphocytes in both C57BL/6 and RAG2(-/-) host chimeric animals. These mice provide a complementary set of in vivo competition assays that formally establish the genetic basis for the rid phenotype. Although the null mutation yields a phenotype quite similar to that of rid, it also compromises expansion of B cell precursors. Our results suggest that the murine and human consequences of Btk deficiency differ only quantitatively, and represent the same disease process.