Nam Hajin, Kim Boyoung, Gautam Avishekh, Kim Yoo Yeon, Park Eun Sun, Lee Jong Sun, Kwon Hyung-Joo, Seong Je Kyung, Suh Jun Gyo
Department of Medical Genetics, College of Medicine, Hallym University, Chuncheon, 24252, Korea.
Department of Microbiology, College of Medicine, Hallym University, Chuncheon, 24252, Korea.
Lab Anim Res. 2022 Sep 8;38(1):28. doi: 10.1186/s42826-022-00138-z.
Inbred mice have several advantages, including genetic similarity to humans, a well-established gene manipulation system, and strong tolerance to inbreeding. However, inbred mice derived from a limited genetic pool have a small genetic diversity. Thus, the development of new inbred strains from wild mice is needed to overcome this limitation. Hence, in this study, we used a new strain of inbred mice called KWM/Hym. We sequenced the Mx1 gene to elucidate the genetic diversities of KWM/Hym mice and observed the biological alterations of the Mx1 protein upon influenza A infection.
The Mx1 gene in KWM/Hym mice had 2, 4, and 38 nucleotide substitutions compared to those in the Mx1 gene in A2G, CAST/EiJ, and Mus spretus mice, respectively. Moreover, the Mx1 protein in KWM/Hym mice had 2 and 25 amino acid substitutions compared to those in the Mx1 protein in CAST/EiJ and M. spretus mice, respectively. To elucidate the function of the Mx1 protein, we inoculated the influenza A virus (A/WSN/1933) in KWM/Hym mice. Nine days after infection, all infected KWM/Hym mice survived without any weight loss. Four days after infection, the lungs of the infected KWM/Hym mice showed mild alveolitis and loss of bronchiolar epithelium; however, the pulmonary viral titers of the infected KWM/Hym mice were significantly lower than that in the infected BALB/c mice (2.17 × plaque-forming units mL).
Our results demonstrate that the KWM/Hym mice are resistant to influenza A virus infection. Further, these mice can be used as a model organism to understand the mechanism of influenza A virus susceptibility.
近交系小鼠具有若干优势，包括与人类的遗传相似性、成熟的基因操作体系以及对近亲繁殖的强耐受性。然而，源自有限基因库的近交系小鼠遗传多样性较小。因此，需要从野生小鼠培育新的近交系以克服这一局限性。于是，在本研究中，我们使用了一种名为KWM/Hym的新型近交系小鼠。我们对Mx1基因进行测序以阐明KWM/Hym小鼠的遗传多样性，并观察甲型流感病毒感染后Mx1蛋白的生物学变化。
与A2G、CAST/EiJ和小家鼠（Mus spretus）的Mx1基因相比，KWM/Hym小鼠的Mx1基因分别有2个、4个和38个核苷酸替换。此外，与CAST/EiJ和小家鼠的Mx1蛋白相比，KWM/Hym小鼠的Mx1蛋白分别有2个和25个氨基酸替换。为阐明Mx1蛋白的功能，我们将甲型流感病毒（A/WSN/1933）接种到KWM/Hym小鼠体内。感染九天后，所有感染的KWM/Hym小鼠均存活且体重未减轻。感染四天后，感染的KWM/Hym小鼠的肺部出现轻度肺泡炎和细支气管上皮脱落；然而，感染的KWM/Hym小鼠的肺病毒滴度显著低于感染的BALB/c小鼠（2.17×噬斑形成单位/毫升）。
我们的结果表明，KWM/Hym小鼠对甲型流感病毒感染具有抗性。此外，这些小鼠可作为模式生物用于了解甲型流感病毒易感性的机制。
