Attempt to identify the responsible gene associated with radiation hypersensitivity of rat

据报道，LEC大鼠表现出X射线过敏性，数量性状基因座(QTL)连锁分析表明，染色体上的特异性区域(Chr)4与X射线过敏性表型有很强的连锁。本研究首先比较了野生型大鼠和LEC大鼠Chr4基因这一区域的几个基因的编码序列，并试图确定推导的氨基酸序列的变化。LEC大鼠的核蛋白NP220(Zfml：ZinFinger，Martin like)是一种DNA结合核蛋白，在编码序列上有单核苷酸替换，并伴随着从苏氨酸到精氨酸的氨基酸替换。为了确定哪种氨基酸替换与辐射敏感性有关，构建了LEC大鼠来源的成纤维细胞，野生型Np220基因，以及携带野生型Np220基因的转基因大鼠，然后进行辐射。然而，这些细胞和转基因大鼠并没有恢复辐射敏感性，这表明NP220不太可能是与X射线过敏相关的负责基因。

The LEC rat has been reported to exhibit X-ray hypersensitivity, and Quantitative trait loci (QTL) linkage analysis revealed that the specific region on Chromosomes (Chr) 4 has a very strong linkage to the X-ray hypersensitive phenotype. The present study was performed as the first step to compare between the coding sequences of several genes located on this region of Chr 4 in the wild type rat and the LEC rat, and to try to identify the changes in deduced amino acid sequences. The NP220 (Zfml: Zinc finger, martin like) gene, the DNA-binding nuclear protein, in the LEC rat has a single nucleotide substitution in the coding sequence accompanied by the amino acid substitution from threonine to arginine. To determine which this amino acid substitution was associated with radiation susceptibility, the fibroblast cells derived from the LEC rat, which were transfected the wild type Np220 cDNA, and the transgenic rats, which were carrying it, were constructed, and then, were irradiated. However, the cells and the transgenic rats have not restored the radiation susceptibility, suggesting that the NP220 was unlikely to be responsible gene associated with X-ray hypersensitivity.