Construction of congenic strain of rat with abnormal NF-kB function and its molecular pathological analysis

Long-Evans Cinnamon(LEC)大鼠是一种遗传性肝炎和自发性肝细胞癌的突变品系。利用永生化肝细胞系93C13(LEC肝细胞)和93A16(对照LEA肝细胞)，寻找LEC大鼠肝脏中缺乏的反式作用因子。基于我们先前发现谷胱甘肽过氧化物酶(GPX1)在LEC大鼠肝脏中的表达持续降低，我们选择了GPX1基因进行分析。瞬时转染分析表明，93C13细胞缺乏与p53和NF-kB协同作用的因子(S)。提示LEC大鼠肝细胞中GPX1表达下降不是由于缺乏特异性转录因子，而是由于碱性转录因子复合体的异常。

The long-Evans Cinnamon (LEC) rat is a mutant strain that develops hereditary hepatitis and spontaneous hepatocellular carcinoma. Using immortalized hepatocyte cell lines, 93C13 (LEC hepatocyte) and 93A16 (control LEA hepatocyte), we searched for a trans-acting factor lacking in the LEC rat liver. Based on our previous finding that glutathione peroxidase (GPx1) expression was consistently reduced in the LEC rat liver, we selected GPx1 gene for its analysis. Transient transfection assays of the constructs containing 5'-flanking sequences fused to the luciferase gene showed that 93C13 cells lacked factor(s) cooperating with p53 and NF-kB. These results suggested that decreased expression of GPx1 in LEC rat hepatocytes is notdue to lack of specific transcription factor but to abnormality in basic transcription factor complex.