Recombinant congenic strains ? A new tool for analyzing genetic traits determined by more than one gene

Démant, Peter; Hart, Andrew

doi:10.1007/bf00377961

Cited by 182 publications

(117 citation statements)

References 39 publications

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“…The AcB/BcA panel of RCS was generated according to a breeding scheme described by Demant and Hart, 35 and have been genotyped for over 600 informative markers. 17 All mice were maintained and handled according to guidelines of the Canadian Council on Animal Care.…”

Section: Methodsmentioning

confidence: 99%

Phenotypic expression of pyruvate kinase deficiency and protection against malaria in a mouse model

Min‐Oo

Fortin

et al. 2004

Genes Immun

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The recombinant congenic mouse strains AcB55 and AcB61 are extremely resistant to malaria (Plasmodium chabaudi AS) despite the presence of susceptibility alleles at the known Char1/Char2 resistance loci. Resistance in AcB55 and AcB61 is controlled by a locus on chromosome 3 (Char4) shown to be allelic with or tightly linked to a loss-of-function mutation in pyruvate kinase (Pklr). AcB55 and AcB61 show important splenomegaly prior to infection caused by the expansion of the red pulp, and display histological signs of extramedullary erythropoiesis in the liver. Examination of splenic cell populations by flow cytometry demonstrates elevated numbers of TER119-positive erythroid precursor cells (430% of total spleen cells), while RNA expression studies show elevated expression of erythrocyte-specific transcripts such as globin, transferrin receptor, and Nramp2/Slc11a2 in the spleen of both strains. Hematological profiling in both strains is consistent with the presence of anemia as evidenced by low total erythrocyte counts, decreased hemoglobin, as well as abnormally high numbers of circulating reticulocytes (15-20%). These results strongly suggest that the mutant Pklr allele (Pklr 269A ) of AcB55/61 strains causes hemolytic anemia compensated by constitutive erythropoiesis, which in turn protects the mice against P. chabaudi infection. The possible molecular basis of the Pklr protective effect is discussed and is under current investigation in these two strains.

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Section: Methodsmentioning

confidence: 99%

Phenotypic expression of pyruvate kinase deficiency and protection against malaria in a mouse model

Min‐Oo

Fortin

et al. 2004

Genes Immun

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“…The type of segregating population that is used in a genetical genomics analysis can improve the power and efficiency of this type of strategy. For example, Demant and Hart 15 proposed the use of RECOMBINANT CONGENIC STRAINS (RCSs) to analyse genetic traits that are determined by more than one gene in the mouse. They generated RCSs in which the fraction of the genome derived from the donor strain was ~12.5%.…”

Section: Refining Genetical Genomicsmentioning

confidence: 99%

Studying complex biological systems using multifactorial perturbation

2003

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“…67 These strains offer a unique opportunity to analyze multigenic traits, as individual resistance/susceptibility loci may independently segregate in individual RCS. They can also be used to characterize the specific phenotypic component of disease susceptibility under genetic control.…”

Section: Studies In Recombinant Congenic Strainsmentioning

confidence: 99%