Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
Eur J Immunol. 2010 Nov;40(11):3161-72. doi: 10.1002/eji.200940221. Epub 2010 Sep 24.
HAX1 was originally described as HS1-associated protein with a suggested function in receptor-mediated apoptotic and proliferative responses of lymphoid cells. Recent publications refer to a complex and multifunctional role of this protein. To investigate the in vivo function of HAX1 (HS1-associated protein X1) in B cells, we generated a Hax1-deficient mouse strain. Targeted deletion of Hax1 resulted in premature death around the age of 12 wk accompanied by a severe reduction of lymphocytes in spleen, thymus and bone marrow. In the bone marrow, all B-cell populations were lost comparably. In the spleen, B220(+) cells were reduced by almost 70%. However, as investigated by adoptive transfer experiments, this impairment is not exclusively B-cell intrinsic and we hypothesize that a HAX1-deficient environment cannot sufficiently provide the essential factors for proper lymphocyte development, trafficking and survival. Hax1(-/-) B cells show a significantly reduced expression of CXCR4, which might have an influence on the observed defects in B-cell development.
HAX1 最初被描述为与 HS1 相关的蛋白，其在淋巴细胞的受体介导的凋亡和增殖反应中具有一定的功能。最近的出版物提到了这种蛋白质的复杂和多功能作用。为了研究 HAX1（HS1 相关蛋白 X1）在 B 细胞中的体内功能，我们生成了 Hax1 缺陷型小鼠品系。Hax1 的靶向缺失导致约 12 周龄时的过早死亡，并伴有脾脏、胸腺和骨髓中淋巴细胞的严重减少。在骨髓中，所有 B 细胞群体的减少都相当。在脾脏中，B220(+)细胞减少了近 70%。然而，如通过过继转移实验所研究的，这种损伤不是 B 细胞内在的，我们假设 HAX1 缺陷环境不能充分提供适当的淋巴细胞发育、迁移和存活所必需的因素。Hax1(-/-)B 细胞显示出 CXCR4 的表达显著降低，这可能对观察到的 B 细胞发育缺陷有影响。
