Laboratory of Laboratory Animal Science and Medicine, Department of Applied Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Laboratory of Laboratory Animal Science and Medicine, Department of Applied Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan; Poultry Production Department, Mansoura University, Mansoura, Egypt.
Infect Genet Evol. 2018 Jan;57:75-81. doi: 10.1016/j.meegid.2017.11.008. Epub 2017 Nov 9.
Sendai virus (SeV) is one of the most important pathogens in the specific-pathogen free rodents. It is known that there are some inbred mouse strains susceptible or resistant to SeV infection. The C57BL/6 (B6) and DBA/2 (D2) mice are representative of the resistant and susceptible strains, respectively. Previous study with the quantitative trait locus (QTL) analysis identified three QTLs responsible for resistance or susceptibility to SeV infection on different chromosomes and indicated that resistance or susceptibility to SeV infection was almost predicted by genotypes of these three QTLs. In this paper, to verify the above hypothesis, congenic lines were generated as follows; B6-congenic lines carrying one of the D2 alleles of three QTLs and combination of these three QTLs, and D2-congenic lines carrying single or combination of B6 alleles of three QTLs. All these congenic lines were then challenged with SeV infection. D2 congenic lines introgressed single or combination of B6 alleles of QTLs changed to resistance to SeV infection. Especially, a D2 triple-congenic line became resistant as similar level to B6-parental strain. However, B6-congenic lines introgressed single or combination of D2 alleles of QTLs all remained to be resistant to SeV infection. Both IL-6 and TNF-α in broncho-alveolar lavage fluid of D2 triple-congenic line were decreased to the similar level of B6 mice, suggesting that this is a part of factors that D2 triple-congenic line became resistant to the similar level of B6 mice. Data obtained from these congenic mice verified that three QTLs identified previously were indeed responsible for the resistance/susceptibility to SeV infection in B6 and D2 mice.
仙台病毒（SeV）是无特定病原体啮齿动物中最重要的病原体之一。已知有一些近交系小鼠对 SeV 感染敏感或有抗性。C57BL/6（B6）和 DBA/2（D2）小鼠分别是抗性和敏感性的代表。先前的定量性状基因座（QTL）分析研究确定了三个负责 SeV 感染抗性或敏感性的 QTL 位于不同染色体上，并表明对 SeV 感染的抗性或敏感性几乎可以由这三个 QTL 的基因型预测。在本文中，为了验证上述假设，生成了以下同系系：携带三个 QTL 中一个 D2 等位基因和这些三个 QTL 的组合的 B6 同系系，以及携带三个 QTL 中一个或组合的 B6 等位基因的 D2 同系系。然后，用 SeV 感染所有这些同系系。D2 同系系引入单个或组合的 B6 等位基因的 QTL 改变为对 SeV 感染的抗性。特别是，D2 三重同系系的抗性与 B6 亲本系相似。然而，B6 同系系引入单个或组合的 D2 等位基因的 QTL 仍然对 SeV 感染具有抗性。D2 三重同系系的支气管肺泡灌洗液中的 IL-6 和 TNF-α 均降低到与 B6 小鼠相似的水平，这表明这是 D2 三重同系系与 B6 小鼠具有相似抗性的部分因素。从这些同系小鼠获得的数据证实了先前鉴定的三个 QTL 确实负责 B6 和 D2 小鼠对 SeV 感染的抗性/敏感性。
