Chromosomal mapping of the host resistance locus to rodent malaria (Plasmodium yoelii) infection in mice

Ohno, Tamio; Ishih, Akira; Kohara, Yuki; Yonekawa, Hiromichi; Terada, Mamoru; Nishimura, Masahiko

doi:10.1007/s00251-001-0390-z

Cited by 34 publications

(29 citation statements)

References 5 publications

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“…This difference in susceptibility to malaria infection between mouse strains has prompted genetic studies in informative backcross and F2 progenies, as well as in recombinant inbred and congenic strains. These studies have confirmed that genetic susceptibility to malaria is indeed complex and have resulted in the mapping of several loci associated with susceptibility to P. chabaudi (Char1-8), [4][5][6][7][8][9] P. yoelii (Pmyr) 10 and P. berghei.…”

Section: Introductionmentioning

confidence: 64%

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Genetic control of parasite clearance leads to resistance to Plasmodium berghei ANKA infection and confers immunity

et al. 2005

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Unprecedented cure after infection with the lethal Plasmodium berghei ANKA was observed in an F2 progeny generated by intercrossing the wild-derived WLA and the laboratory C57BL/6 mouse strains. Resistant mice were able to clear parasitaemia and establish immunity. The observed resistance was disclosed as a combinatorial effect of genetic factors derived from the two parental strains. Genetic mapping of survival time showed that the WLA allele at a locus on chromosome 1 (colocalizing with Berghei resistance 1 (Berr1), a locus associated with resistance to experimental cerebral malaria) increases the probability to resist early death. Also, the C57Bl/6 allele at a novel locus on chromosome 9 (Berr3) confers overall resistance to this lethal Plasmodium infection. This report underlines the value of using wild-derived mouse strains to identify novel genetic factors in the aetiology of disease phenotypes, and provides a unique model for studying parasite clearance and immunity associated with malaria.

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Section: Introductionmentioning

confidence: 64%

“…10 An over-representation of the WLA allele at this locus was observed among the mice that resisted early death (Table 3). In fact, only 5.3% of the mice that died early (before 13 days postinfection) were homozygous for the WLA allele, while 55% were C57BL/6 homozygous at the marker D1Mit221.…”

Section: Resultsmentioning

confidence: 99%

Genetic control of parasite clearance leads to resistance to Plasmodium berghei ANKA infection and confers immunity

et al. 2005

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“…The peak LOD score was identified at 59.7 Mb (for marker rs9_6; NCBI ID: rs3685575). Char10 is proximal to the P. chabaudi resistance locus, Char1, which has been previously localized around position 100 Mb 36,37 ( Figure 6a). Subsequent analysis of chromosome 9 using additional mice from a fourth batch of F2 mice (n ¼ 237 total; males ¼ 140, females ¼ 97) and a subset of microsatellite markers, increased the LOD score to 10.8 and decreased the 95% credible interval to 17 Mb, from 51.3 to 68.3 Mb (Supplementary Figure 2).…”

Section: Iron Overload In Acb62 Tissuesmentioning

confidence: 99%

Mapping of Char10, a novel malaria susceptibility locus on mouse chromosome 9

Min‐Oo¹,

Willemetz²,

Tam³

et al. 2009

Genes Immun

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Resistance to blood-stage malaria in AcB55 and AcB61 is caused by a loss of function mutation in pyruvate kinase (Pklr I90N ). Likewise, pyruvate kinase (PK) deficiency in humans is protective against Plasmodium replication in vitro. We identified a third AcB strain, AcB62 that also carries the Pklr I90N mutation. However, AcB62 mice were susceptible to P.chabaudi infection and showed high levels of parasite replication (54-62% peak parasitemia). AcB62 mice showed the hallmarks of PK deficiencyassociated anemia similar to AcB55/61 with reticulocytosis, splenic red pulp expansion, tissue iron overload, and increased expression of iron metabolism proteins. This suggests that malaria susceptibility in AcB62 is not because of absence of PK deficiency-associated pathophysiology. To map novel genetic factors affecting malaria susceptibility in AcB62, we generated an informative F2 population using AcB62 (Pklr I90N ) and CBA-Pk slc (Pklr G338D ) as progenitors and identified a novel locus on chromosome 9 (Char10; LOD ¼ 7.24) that controls peak parasitemia. A weaker linkage to the Pklr region of chromosome 3 (LOD ¼ 3.7) was also detected, a finding that may reflect the segregation of the two defective Pklr alleles. AcB62 alleles at both loci are associated with higher peak parasitemia. These results identify Char10 as a novel locus modulating severity of malaria in the context of PK deficiency.

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“…46,47 In an early study, it was shown that the BALB/c.D2 congenic mouse strain (congenic for the mtv-7 locus, located on the distal region of chromosome 1) exhibits an altered susceptibility phenotype to the parental BALB/c line, suggesting that this locus is involved in resistance to P .yoelii infection. 48 Ohno and colleagues 49 have reported the results of a genome-wide search for resistance QTL to P. yoelii infection. Their study was conducted in a BC resource population.…”

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confidence: 99%

African Trypanosomiasis

2008

Encyclopedia of Public Health

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Malaria and trypanosomiasis are vector-borne protozoal diseases which disproportionately affect the poor. Both give rise to immense human suffering; malaria exerts its effect directly on human health, while trypanosomiasis causes damage largely though its effect on the health and productivity of the livestock on which so many poor people depend. These diseases both have multifaceted and poorly understood mechanisms of pathogenesis, combined with relatively complex life cycles characterised by multiple stages in both insect vector and mammalian host. In both cases, there is a dramatic effect of host genotype on disease progression. This effect is apparent in both the human and cattle hosts and among inbred mouse strains. This provides an opportunity to use the mouse to probe the mechanisms underlying resistance or susceptibility to pathology. The availability of high-density linkage maps, the genome sequence and transcriptomics tools has transformed the power of the mouse to illuminate such fundamental aspects of the host-parasite interaction.

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Chromosomal mapping of the host resistance locus to rodent malaria (Plasmodium yoelii) infection in mice

Cited by 34 publications

References 5 publications

Genetic control of parasite clearance leads to resistance to Plasmodium berghei ANKA infection and confers immunity

Genetic control of parasite clearance leads to resistance to Plasmodium berghei ANKA infection and confers immunity

Mapping of Char10, a novel malaria susceptibility locus on mouse chromosome 9

African Trypanosomiasis

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