Kerner J D, Appleby M W, Mohr R N, Chien S, Rawlings D J, Maliszewski C R, Witte O N, Perlmutter R M
Department of Immunology, University of Washington, Seattle 98195, USA.
Immunity. 1995 Sep;3(3):301-12. doi: 10.1016/1074-7613(95)90115-9.
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 (xid). 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 xid phenotype. Although the null mutation yields a phenotype quite similar to that of xid, 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.
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连锁无丙种球蛋白血症（XLA）相关。在小鼠中，Btk普列克底物蛋白同源结构域中的一个点突变与一种较为温和的X连锁免疫缺陷（xid）相关联。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。这些小鼠提供了一组互补的体内竞争试验，正式确立了xid表型的遗传基础。虽然无效突变产生的表型与xid非常相似，但它也损害了B细胞前体的扩增。我们的结果表明，Btk缺陷在小鼠和人类中的后果仅在数量上有所不同，代表相同的疾病过程。
