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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

A Parent-of-Origin Effect Determines the Susceptibility of a Non-Informative F1 Population to Trypanosoma cruzi Infection In Vivo

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Autor(es):
Silva, Grace K. [1, 2] ; Cunha, Larissa D. [1] ; Horta, Catarina V. [1] ; Silva, Alexandre L. N. [1] ; Gutierrez, Fredy R. S. [2] ; Silva, Joao S. [2] ; Zamboni, Dario S. [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Cell Biol, FMRP USP, Sao Paulo - Brazil
[2] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Biochem & Immunol, FMRP USP, Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 8, n. 2 FEB 11 2013.
Citações Web of Science: 10
Resumo

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. (AU)

Processo FAPESP: 10/50959-4 - Determinação de loci e genes de camundongos responsáveis pela resistência natural à infecção por Trypanosoma cruzi
Beneficiário:Dario Simões Zamboni
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 07/53940-0 - Células T reguladoras e TH 17 no controle da imunidade contra infecções, tumores e doenças autoimunes
Beneficiário:João Santana da Silva
Linha de fomento: Auxílio à Pesquisa - Temático