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Genetic Control of Resistance to Trypanosoma brucei brucei Infection in Mice

BACKGROUND: Trypanosoma brucei brucei infects livestock, with severe effects in horses and dogs. Mouse strains differ greatly in susceptibility to this parasite. However, no genes controlling these differences were mapped. METHODS: We studied the genetic control of survival after T. b. brucei infect...

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Autores principales: Šíma, Matyáš, Havelková, Helena, Quan, Lei, Svobodová, Milena, Jarošíková, Taťána, Vojtíšková, Jarmila, Stassen, Alphons P. M., Demant, Peter, Lipoldová, Marie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110168/
https://www.ncbi.nlm.nih.gov/pubmed/21666791
http://dx.doi.org/10.1371/journal.pntd.0001173
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author Šíma, Matyáš
Havelková, Helena
Quan, Lei
Svobodová, Milena
Jarošíková, Taťána
Vojtíšková, Jarmila
Stassen, Alphons P. M.
Demant, Peter
Lipoldová, Marie
author_facet Šíma, Matyáš
Havelková, Helena
Quan, Lei
Svobodová, Milena
Jarošíková, Taťána
Vojtíšková, Jarmila
Stassen, Alphons P. M.
Demant, Peter
Lipoldová, Marie
author_sort Šíma, Matyáš
collection PubMed
description BACKGROUND: Trypanosoma brucei brucei infects livestock, with severe effects in horses and dogs. Mouse strains differ greatly in susceptibility to this parasite. However, no genes controlling these differences were mapped. METHODS: We studied the genetic control of survival after T. b. brucei infection using recombinant congenic (RC) strains, which have a high mapping power. Each RC strain of BALB/c-c-STS/A (CcS/Dem) series contains a different random subset of 12.5% genes from the parental “donor” strain STS/A and 87.5% genes from the “background” strain BALB/c. Although BALB/c and STS/A mice are similarly susceptible to T. b. brucei, the RC strain CcS-11 is more susceptible than either of them. We analyzed genetics of survival in T. b. brucei-infected F(2) hybrids between BALB/c and CcS-11. CcS-11 strain carries STS-derived segments on eight chromosomes. They were genotyped in the F(2) hybrid mice and their linkage with survival was tested by analysis of variance. RESULTS: We mapped four Tbbr (Trypanosoma brucei brucei response) loci that influence survival after T. b. brucei infection. Tbbr1 (chromosome 3) and Tbbr2 (chromosome 12) have effects on survival independent of inter-genic interactions (main effects). Tbbr3 (chromosome 7) influences survival in interaction with Tbbr4 (chromosome 19). Tbbr2 is located on a segment 2.15 Mb short that contains only 26 genes. CONCLUSION: This study presents the first identification of chromosomal loci controlling susceptibility to T. b. brucei infection. While mapping in F(2) hybrids of inbred strains usually has a precision of 40–80 Mb, in RC strains we mapped Tbbr2 to a 2.15 Mb segment containing only 26 genes, which will enable an effective search for the candidate gene. Definition of susceptibility genes will improve the understanding of pathways and genetic diversity underlying the disease and may result in new strategies to overcome the active subversion of the immune system by T. b. brucei.
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spelling pubmed-31101682011-06-10 Genetic Control of Resistance to Trypanosoma brucei brucei Infection in Mice Šíma, Matyáš Havelková, Helena Quan, Lei Svobodová, Milena Jarošíková, Taťána Vojtíšková, Jarmila Stassen, Alphons P. M. Demant, Peter Lipoldová, Marie PLoS Negl Trop Dis Research Article BACKGROUND: Trypanosoma brucei brucei infects livestock, with severe effects in horses and dogs. Mouse strains differ greatly in susceptibility to this parasite. However, no genes controlling these differences were mapped. METHODS: We studied the genetic control of survival after T. b. brucei infection using recombinant congenic (RC) strains, which have a high mapping power. Each RC strain of BALB/c-c-STS/A (CcS/Dem) series contains a different random subset of 12.5% genes from the parental “donor” strain STS/A and 87.5% genes from the “background” strain BALB/c. Although BALB/c and STS/A mice are similarly susceptible to T. b. brucei, the RC strain CcS-11 is more susceptible than either of them. We analyzed genetics of survival in T. b. brucei-infected F(2) hybrids between BALB/c and CcS-11. CcS-11 strain carries STS-derived segments on eight chromosomes. They were genotyped in the F(2) hybrid mice and their linkage with survival was tested by analysis of variance. RESULTS: We mapped four Tbbr (Trypanosoma brucei brucei response) loci that influence survival after T. b. brucei infection. Tbbr1 (chromosome 3) and Tbbr2 (chromosome 12) have effects on survival independent of inter-genic interactions (main effects). Tbbr3 (chromosome 7) influences survival in interaction with Tbbr4 (chromosome 19). Tbbr2 is located on a segment 2.15 Mb short that contains only 26 genes. CONCLUSION: This study presents the first identification of chromosomal loci controlling susceptibility to T. b. brucei infection. While mapping in F(2) hybrids of inbred strains usually has a precision of 40–80 Mb, in RC strains we mapped Tbbr2 to a 2.15 Mb segment containing only 26 genes, which will enable an effective search for the candidate gene. Definition of susceptibility genes will improve the understanding of pathways and genetic diversity underlying the disease and may result in new strategies to overcome the active subversion of the immune system by T. b. brucei. Public Library of Science 2011-06-07 /pmc/articles/PMC3110168/ /pubmed/21666791 http://dx.doi.org/10.1371/journal.pntd.0001173 Text en Šíma et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Šíma, Matyáš
Havelková, Helena
Quan, Lei
Svobodová, Milena
Jarošíková, Taťána
Vojtíšková, Jarmila
Stassen, Alphons P. M.
Demant, Peter
Lipoldová, Marie
Genetic Control of Resistance to Trypanosoma brucei brucei Infection in Mice
title Genetic Control of Resistance to Trypanosoma brucei brucei Infection in Mice
title_full Genetic Control of Resistance to Trypanosoma brucei brucei Infection in Mice
title_fullStr Genetic Control of Resistance to Trypanosoma brucei brucei Infection in Mice
title_full_unstemmed Genetic Control of Resistance to Trypanosoma brucei brucei Infection in Mice
title_short Genetic Control of Resistance to Trypanosoma brucei brucei Infection in Mice
title_sort genetic control of resistance to trypanosoma brucei brucei infection in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110168/
https://www.ncbi.nlm.nih.gov/pubmed/21666791
http://dx.doi.org/10.1371/journal.pntd.0001173
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