A parent-of-origin effect determines the susceptibility of a non-informative F1 population to Trypanosoma cruzi infection in vivo.
A parent-of-origin effect determines the susceptibility of a non-informative F1 population to Trypanosoma cruzi infection in vivo.
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DOI：
10.1371/journal.pone.0056347
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zamboni DS
中科院分区：
文献类型：
--
作者：
Silva GK;Cunha LD;Horta CV;Silva AL;Gutierrez FR;Silva JS;Zamboni DS
恰加斯病的发展是由原生动物寄生虫，T。cruzi和被感染的宿主这一过程由多个基因调控，这些基因控制宿主-寄生虫相互作用的不同方面。虽然在人类中确定相关基因是极其困难的，但使用近交系小鼠品系来确定负责宿主对感染的抗性的基因和位点是可行的。在这项研究中，我们调查了几个近交系小鼠品系对T. cruzi等人的研究发现，A/J和C57 BL/6小鼠之间的易感性存在相当大的差异。我们探讨了这两种小鼠品系之间的差异，发现A/J品系的死亡率更高，寄生虫血症加剧和不受控制，靶器官的组织病理学特征明显，这与寄生虫负荷更高和组织病变更广泛有关。然后，我们采用了遗传方法来评估在F1代人口的抗性表型的遗传模式，并检测到一个强大的父母的原产地的影响，确定F1代雄性小鼠的易感性。这种效应不太可能来自印记基因，因为这种易感性的遗传受到亲本杂交方向的影响。总的来说，我们使用F1群体的遗传方法表明，小鼠X染色体中包含的基因有助于对T的天然抗性。克氏感染未来的连锁研究可能会揭示参与本文报道的宿主抗性过程的位点和基因。
The development of Chagas disease is determined by a complex interaction between the genetic traits of both the protozoan parasite, T. cruzi, and the infected host. This process is regulated by multiple genes that control different aspects of the host-parasite interaction. While determination of the relevant genes in humans is extremely difficult, it is feasible to use inbred mouse strains to determine the genes and loci responsible for host resistance to infection. In this study, we investigated the susceptibility of several inbred mouse strains to infection with the highly virulent Y strain of T. cruzi and found a considerable difference in susceptibility between A/J and C57BL/6 mice. We explored the differences between these two mouse strains and found that the A/J strain presented higher mortality, exacerbated and uncontrolled parasitemia and distinct histopathology in the target organs, which were associated with a higher parasite burden and more extensive tissue lesions. We then employed a genetic approach to assess the pattern of inheritance of the resistance phenotype in an F1 population and detected a strong parent-of-origin effect determining the susceptibility of the F1 male mice. This effect is unlikely to result from imprinted genes because the inheritance of this susceptibility was affected by the direction of the parental crossing. Collectively, our genetic approach of using the F1 population suggests that genes contained in the murine chromosome X contribute to the natural resistance against T. cruzi infection. Future linkage studies may reveal the locus and genes participating on the host resistance process reported herein.
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