FAT10/diubiquitin-like protein-deficient mice exhibit minimal phenotypic differences
FAT10/diubiquitin-like protein-deficient mice exhibit minimal phenotypic differences
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DOI：
10.1128/mcb.00966-05
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发表时间：
2006-07-01
影响因子：
5.3
通讯作者：
Weissman, Sherman M.
中科院分区：
文献类型：
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作者：
Canaan, Allon;Yu, Xiaofeng;Weissman, Sherman M.
FAT 10基因编码一个双泛素样蛋白，含有两个串联的头-尾泛素样结构域。在mRNA和蛋白质水平上，鼠和人FAT 10序列之间存在高度相似性。在各种细胞系中，FAT 10的表达被证明是由γ干扰素或肿瘤坏死因子α诱导的。此外，发现FAT 10表达在一些EB病毒感染的B细胞系、活化的树突状细胞和几种上皮肿瘤中上调。然而，也发现在培养的细胞中FAT 10的强制表达产生凋亡性细胞死亡。总之，这些发现表明，FAT 10可以调节细胞生长或细胞活力。在这里，我们描述了通过遗传靶向产生FAT 10基因敲除小鼠模型的步骤。FAT 10基因敲除纯合子小鼠存活且可生育。在这些突变小鼠中未发现肉眼病变或明显的组织学差异。对脾脏、胸腺和骨髓的淋巴细胞群进行检查未发现任何异常。然而，流式细胞术分析表明，平均而言，FAT 10敲除小鼠的淋巴细胞更容易发生自发性凋亡。在生理学上，这些小鼠表现出对内毒素攻击的高水平敏感性。这些发现表明，FAT 10可能是一个生存因子。
The FAT10 gene encodes a diubiquitin-like protein containing two tandem head-to-tail ubiquitin-like domains. There is a high degree of similarity between murine and human FAT10 sequences at both the mRNA and protein levels. In various cell lines, FAT10 expression was shown to be induced by gamma interferon or by tumor necrosis factor alpha. In addition, FAT10 expression was found to be up-regulated in some Epstein-Barr virus-infected B-cell lines, in activated dendritic cells, and in several epithelial tumors. However, forced expression of FAT10 in cultured cells was also found to produce apoptotic cell death. Overall, these findings suggest that FAT10 may modulate cellular growth or cellular viability. Here we describe the steps to generate, by genetic targeting, a FAT10 gene knockout mouse model. The FAT10 knockout homozygous mice are viable and fertile. No gross lesions or obvious histological differences were found in these mutated mice. Examination of lymphocyte populations from spleen, thymus, and bone marrow did not reveal any abnormalities. However, How cytometry analysis demonstrated that the lymphocytes of FAT10 knockout mice were, on average, more prone to spontaneous apoptotic death. Physiologically, these mice demonstrated a high level of sensitivity toward endotoxin challenge. These findings indicate that FAT10 may function as a survival factor.