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首页> 外文期刊>Molecular and Cellular Biology >Influenza virus-susceptible mice carry Mx genes with a large deletion or a nonsense mutation.
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Influenza virus-susceptible mice carry Mx genes with a large deletion or a nonsense mutation.

机译：易感流感病毒的小鼠携带带有大缺失或无意义突变的Mx基因。

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The interferon-regulated mouse Mx gene encodes the 72-kilodalton nuclear Mx protein that selectively inhibits influenza virus replication. Mice carrying Mx+ alleles synthesize Mx protein and resist influenza virus infection, whereas mice homozygous for Mx- alleles fail to synthesize Mx protein and, as a consequence, are influenza virus susceptible. Southern blot analysis allowed us to define the following three distinct Mx restriction fragment length polymorphism (RFLP) types among classical inbred strains: RFLP type 1 in the Mx+ strains A2G and SL/NiA, RFLP type 2 in BALB/c and 33 other Mx- strains, and RFLP type 3 in CBA/J and 2 other Mx- strains. cDNA clones of Mx mRNAs from BALB/c and CBA/J cells were isolated, and their sequences were compared with that of the wild-type Mx mRNA of strain A2G. Mx mRNA of BALB/c mice has 424 nucleotides absent from the coding region, resulting in a frame shift and premature termination of Mx protein. The missing sequences correspond exactly to Mx exons 9 through 11. These three exons, together with some flanking intron sequences, are deleted from the genomes of all Mx RFLP type 2 strains. The Mx- phenotype of the Mx RFLP type 3 strain CBA/J is due to a point mutation that converts the lysine codon in position 389 to a termination codon. Mx RFLP type 3 strains have an extra HindIII site which maps to an intron and thus probably does not affect the coding capacity of Mx mRNA. We further show that the Mx mRNA levels in interferon-treated BALB/c and CBA/J cells are about 15-fold lower than in similarly treated Mx+ cells. This is probably due to decreased metabolic stabilities of the mutant mRNAs.
机译：干扰素调节的小鼠Mx基因编码72千达尔顿核Mx蛋白，该蛋白选择性抑制流感病毒复制。携带Mx +等位基因的小鼠合成Mx蛋白并抵抗流感病毒感染，而纯合Mx-等位基因的小鼠则无法合成Mx蛋白，因此易感流感病毒。 Southern印迹分析使我们能够在经典近交菌株中定义以下三种不同的Mx限制性片段长度多态性（RFLP）类型：Mx +菌株A2G和SL / NiA中的RFLP类型1，BALB / c中的RFLP 2类型和33个其他Mx-菌株，以及CBA / J中的RFLP 3型和其他2种Mx-菌株。分离了来自BALB / c和CBA / J细胞的Mx mRNA的cDNA克隆，并将其序列与菌株A2G的野生型Mx mRNA的序列进行比较。 BALB / c小鼠的Mx mRNA编码区域缺少424个核苷酸，导致Mx蛋白移码和过早终止。缺失的序列正好对应于Mx外显子9至11。这三个外显子以及一些侧翼内含子序列从所有Mx RFLP 2型菌株的基因组中删除。 Mx RFLP 3型菌株CBA / J的Mx表型归因于将389位赖氨酸密码子转化为终止密码子的点突变。 Mx RFLP 3型菌株具有一个额外的HindIII位点，该位点映射到一个内含子，因此可能不影响Mx mRNA的编码能力。我们进一步显示，干扰素处理的BALB / c和CBA / J细胞中的Mx mRNA水平比类似处理的Mx +细胞低约15倍。这可能是由于突变的mRNA的代谢稳定性下降所致。

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