X染色体上的一个Cmv2数量性状基因座影响新西兰雄性小鼠对巨细胞病毒的抗性。
A Cmv2 QTL on chromosome X affects MCMV resistance in New Zealand male mice.
作者信息
Rodriguez Marisela R, Lundgren Alyssa, Sabastian Pearl, Li Qian, Churchill Gary, Brown Michael G
机构信息
Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
出版信息
Mamm Genome. 2009 Jul;20(7):414-23. doi: 10.1007/s00335-009-9203-8. Epub 2009 Jul 30.
NK cell-mediated resistance to viruses is subject to genetic control in humans and mice. Here we used classical and quantitative genetic strategies to examine NK-mediated murine cytomegalovirus (MCMV) control in genealogically related New Zealand white (NZW) and black (NZB) mice. NZW mice display NK cell-dependent MCMV resistance while NZB NK cells fail to limit viral replication after infection. Unlike Ly49H(+) NK resistance in C57BL/6 mice, NZW NK-mediated MCMV control was Ly49H-independent. Instead, MCMV resistance in NZW (Cmv2) involves multiple genetic factors. To establish the genetic basis of Cmv2 resistance, we further characterized a major chromosome X-linked resistance locus (DXMit216) responsible for innate MCMV control in NZW x NZB crosses. We found that the DXMit216 locus affects early MCMV control in New Zealand F(2) crosses and demonstrate that the NZB-derived DXMit216 allele enhances viral resistance in F(2) males. The evolutionary conservation of the DXMit216 region in mice and humans suggests that a Cmv2-related mechanism may affect human antiviral responses.
自然杀伤（NK）细胞介导的抗病毒作用在人类和小鼠中均受基因控制。在此，我们运用经典遗传学和数量遗传学策略，研究了基因谱系相关的新西兰白兔（NZW）和黑兔（NZB）小鼠中NK介导的鼠巨细胞病毒（MCMV）控制情况。NZW小鼠表现出NK细胞依赖性的MCMV抗性，而NZB小鼠的NK细胞在感染后无法限制病毒复制。与C57BL/6小鼠中Ly49H(+) NK抗性不同，NZW小鼠中NK介导的MCMV控制不依赖Ly49H。相反，NZW小鼠（Cmv2）中的MCMV抗性涉及多个遗传因素。为确定Cmv2抗性的遗传基础，我们进一步对一个主要的X染色体连锁抗性位点（DXMit216）进行了特征分析，该位点负责NZW×NZB杂交后代对MCMV的先天性控制。我们发现DXMit216位点影响新西兰F(2)杂交后代对MCMV的早期控制，并证明NZB来源的DXMit216等位基因增强了F(2)雄性小鼠的病毒抗性。小鼠和人类中DXMit216区域的进化保守性表明，一种与Cmv2相关的机制可能影响人类的抗病毒反应。
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