Association of a Determinant on Mouse Chromosome 18 with Experimental Severe<i>Plasmodium berghei</i>Malaria

Nagayasu, Eiji; Nagakura, Kouichi; Akaki, Mayumi; Tamiya, Gen; Makino, Satoshi; Nakano, Yamaji; Kimura, Minoru; Aikawa, Masamichi

doi:10.1128/iai.70.2.512-516.2002

Cited by 31 publications

(16 citation statements)

References 20 publications

(16 reference statements)

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“…The WLA alleles at both these loci confer resistance to ECM, because it is over-represented among the resistant individual (in 67.0% for Berr1 and 64.9% for Berr2 in 94 ECM resistant mice). In fact, these results differ markedly from those of a study that used the DBA͞2 laboratory strain and reported that a locus on chromosome 18 was found to confer resistance to death by a severe form of malaria induced by infection with P. berghei ANKA (24). Although is not clear whether this locus controls resistance to CM, the recent research on the genetics of murine malaria shows that the diversity of resistance loci reported by different laboratories may reflect the use of different parasite strains, mouse strains, and disease phenotypic manifestations.…”

Section: Discussioncontrasting

confidence: 56%

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Identification of two cerebral malaria resistance loci using an inbred wild-derived mouse strain

Bagot

Campino

Penha‐Gonçalves

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Malaria is a complex infectious disease in which the host͞parasite interaction is strongly influenced by host genetic factors. The consequences of plasmodial infections range from asymptomatic to severe complications like the neurological syndrome cerebral malaria induced by Plasmodium falciparum in humans and Plasmodium berghei ANKA in rodents. Mice infected with P. berghei ANKA show marked differences in disease manifestation and either die from experimental cerebral malaria (ECM) or from hemolytic anemia caused by hyperparasitemia (HP). A majority of laboratory mouse strains so far investigated are susceptible to ECM; however, a number of wild-derived inbred strains show resistance. To evaluate the genetic basis of this difference, we crossed a uniquely ECM-resistant, wild-derived inbred strain (WLA) with an ECM susceptible laboratory strain (C57BL͞6J). All of the (WLA ؋ C57BL͞6J) F 1 and 97% of the F2 progeny displayed ECM resistance similar to the WLA strain. To screen for loci contributing to ECM resistance, we analyzed a cohort of mice backcrossed to the C57BL͞6J parental strain. A genome wide screening of this cohort provided significant linkage of ECM resistance to marker loci in two genetic regions on chromosome 1 ( 2 ‫؍‬ 18.98, P ‫؍‬ 1.3 ؋ 10 ؊5 ) and on chromosome 11 ( 2 ‫؍‬ 16.51, P ‫؍‬ 4.8 ؋ 10 ؊5 ), being designated Berr1 and Berr2, respectively. These data provide the first evidence of loci associated with resistance to murine cerebral malaria, which may have important implications for the search for genetic factors controlling cerebral malaria in humans.

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Section: Discussioncontrasting

confidence: 56%

“…Thus, using a F 2 generation from a cross between two laboratory strains, the susceptible C57BL͞6J and a relatively resistant strain DBA͞2, a locus on chromosome 18 was reported to be associated with resistance to experimental severe malaria (24).…”

mentioning

confidence: 99%

Identification of two cerebral malaria resistance loci using an inbred wild-derived mouse strain

Bagot

Campino

Penha‐Gonçalves

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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“…For example, the resistance of F1 intercrossed BALB/c (resistant) and C57BL/6 (susceptible) mice to the development of ECM is determined by age, and environmental exposure, with young mice (8-10 weeks) susceptible to ECM and older mice (16-20 weeks) resistant to the development of cerebral signs (Hearn et al 2000). Genetic resistance to ECM and P. berghei ANKA infection has been mapped using intercrossed resistant and susceptible strains of mice to loci on chromosomes 1, 9, 11, 17 and 18 (Bagot et al 2002 ;Nagayasu et al 2002 ;Ohno and Nishimura, 2004 ;Campino et al 2005). However, the genes encoded within each of these regions that control resistance to ECM and parasite levels remain to be identified.…”

Section: Plasmodium Berghei Ankamentioning

confidence: 99%

Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease

et al. 2009

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Cerebral malaria is a life-threatening complication of malaria infection. The pathogenesis of cerebral malaria is poorly defined and progress in understanding the condition is severely hampered by the inability to study in detail, ante-mortem, the parasitological and immunological events within the brain that lead to the onset of clinical symptoms. Experimental murine models have been used to investigate the sequence of events that lead to cerebral malaria, but there is significant debate on the merits of these models and whether their study is relevant to human disease. Here we review the current understanding of the parasitological and immunological events leading to human and experimental cerebral malaria, and explain why we believe that studies with experimental models of CM are crucial to define the pathogenesis of the condition.

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“…Recently, Nagayasu and colleagues 42 published the first results of a genomewide scan for resistant QTL to P. berghei infection using an F2 intercross population generated from moderate resistant, DBA/2, and susceptible, C57BL/6, mouse strains. They showed a single significant QTL associated with resistance on chromosome 18 (Mmu18).…”

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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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Association of a Determinant on Mouse Chromosome 18 with Experimental SeverePlasmodium bergheiMalaria

Cited by 31 publications

References 20 publications

Identification of two cerebral malaria resistance loci using an inbred wild-derived mouse strain

Identification of two cerebral malaria resistance loci using an inbred wild-derived mouse strain

Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease

African Trypanosomiasis

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