Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1
Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1
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DOI：
10.1073/pnas.95.24.14395
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发表时间：
1998-11-24
影响因子：
11.1
通讯作者：
Alexander, WS
中科院分区：
文献类型：
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作者：
Starr, R;Metcalf, D;Alexander, WS
SOCS-1是细胞因子信号转导抑制因子（SOCS）家族的成员，在白细胞介素6信号转导抑制剂的遗传筛选中被鉴定，SOCS-1转录由细胞因子诱导，并且该蛋白质结合并抑制Janus激酶，并减少白细胞介素6受体的信号转导和转录激活因子3和gp 130组分的酪氨酸磷酸化。因此，SOCS-1形成调节来自细胞因子受体的信号转导的反馈环的一部分。为了检查SOCS-1在体内的作用，我们使用基因靶向来产生缺乏该蛋白的小鼠，SOCS-1（-/-）小鼠表现出生长迟缓，并且在断奶前死亡，伴有肝脏的脂肪变性和几个器官的单核细胞浸润。此外，SOCS-1（-/-）小鼠的胸腺明显缩小，骨髓、脾脏和外周血中成熟B淋巴细胞逐渐减少。因此，SOCS-1是体内调节多种细胞类型所必需的，并且是正常出生后生长和存活所不可或缺的。
SOCS-1, a member of the suppressor of cytokine signaling (SOCS) family, was identified in a genetic screen for inhibitors of interleukin 6 signal transduction, SOCS-1 transcription is induced by cytokines, and the protein binds and inhibits Janus kinases and reduces cytokine-stimulated tyrosine phosphorylation of signal transducers and activators of transcription 3 and the gp130 component of the interleukin 6 receptor. Thus, SOCS-1 forms part of a feedback loop that modulates signal transduction from cytokine receptors, To examine the role of SOCS-1 in vivo, we have used gene targeting to generate mice lacking this protein, SOCS-1(-/-) mice exhibited stunted growth and died before weaning with fatty degeneration of the liver and monocytic infiltration of several organs. In addition, the thymus of SOCS-1(-/-) mice was reduced markedly in size, and there was a progressive loss of maturing B lymphocytes in the bone marrow, spleen, and peripheral blood. Thus, SOCS-1 is required for in vivo regulation of multiple cell types and is indispensable for normal postnatal growth and survival.