Genetic inactivation of the allograft inflammatory factor-1 locus.

Genetic inactivation of the allograft inflammatory factor-1 locus.
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DOI:
10.1002/dvg.22424
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发表时间:
2013-10
期刊:
影响因子:
1.5
通讯作者:
Sibinga, Nicholas E. S.
Sibinga, Nicholas E. S.
中科院分区:
生物学4区
文献类型:
--
作者:
Casimiro, Isabel;Chinnasamy, Prameladevi;Sibinga, Nicholas E. S.

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同种异体移植炎性因子-1(Allograft inflammatory factor-1,Aif-1)是一种17 kDa的EF手型结构蛋白,主要表达于精子细胞和单核/巨噬细胞系。Aif-1表达增加已在临床上重要的疾病中被鉴定,包括类风湿性关节炎、系统性硬化症、子宫内膜异位症和移植相关动脉硬化。从相同位点产生的类似基因产物被称为离子化Ca 2+结合衔接子-1(Iba 1)、小胶质细胞反应因子-1(MRF 1)和daintain; Iba 1特别是已成为小胶质细胞及其在病理性CNS条件下活化的组织学标志物,包括对面神经轴突切断术和中风、葡萄膜炎以及实验性自身免疫性神经炎和脑脊髓炎的反应。尽管如此,aif-1基因产物如何影响细胞功能还只是部分了解,这些产物对男性生育力、免疫系统发育和炎症的生理意义还没有被描述。为了允许这样的研究,我们产生了一个小鼠品系,有针对性地删除了aif-1基因的编码区。在这里,我们报告说,缺乏Aif-1的小鼠繁殖良好,并显示正常的出生后生长,但在胶原诱导的关节炎模型中显示出对疾病的抵抗力。我们预计,这些小鼠将有助于研究Aif-1在各种免疫和炎症疾病模型中的功能。
Allograft inflammatory factor-1 (Aif-1) is a 17 kDa EF hand motif-bearing protein expressed primarily in developing spermatids and cells of monocyte/macrophage lineage. Increased Aif-1 expression has been identified in clinically important conditions, including rheumatoid arthritis, systemic sclerosis, endometriosis, and transplant-associated arteriosclerosis. Largely similar gene products arising from the same locus are known as ionized Ca2+ binding adapter-1 (Iba1), microglial response factor-1 (MRF1), and daintain; Iba1 in particular has emerged as a histologic marker of microglia and their activation in pathologic CNS conditions, including the response to facial nerve axotomy and stroke, uveitis, and experimental autoimmune neuritis and encephalomyelitis. Nevertheless, how aif-1 gene products affect cellular function is only partly understood, and the physiologic significance of these products for male fertility, immune system development, and inflammation has not been described. To permit such investigations, we generated a mouse line with targeted deletion of the coding regions of the aif-1 gene. Here we report that mice lacking Aif-1 breed well and show normal post-natal growth, but show resistance to disease in a model of collagen-induced arthritis. We anticipate that these mice will be useful for studies of Aif-1 function in a variety of immune and inflammatory disease models.
DOI: 10.1006/bbrc.1996.1112
发表时间: 1996-07-25
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