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BXSB/long-lived is a recombinant inbred strain containing powerful disease suppressor loci

Haywood, M. E.
Gabriel, Luisa
Rose, S. J.
Rogers, N. J.
Morley, B. J.
Published in Journal of Immunology. 2007, vol. 179, no. 4, p. 2428-2434
Abstract The BXSB strain of recombinant inbred mice develops a spontaneous pathology that closely resembles the human disease systemic lupus erythematosus. Six non-MHC loci, Yaa, Bxs1-4, and Bxs6, have been linked to the development of aspects of the disease while a further locus, Bxs5, may be a BXSB-derived disease suppressor. Disease development is delayed in a substrain of BXSB, BXSB/MpJScr-long-lived (BXSB/ll). We compared the genetic derivation of BXSB/ll mice to the original strain, BXSB/MpJ, using microsatellite markers and single nucleotide polymorphisms across the genome. These differences were clustered and included two regions known to be important in the disease-susceptibility of these mice, Bxs5 and 6, as well as regions on chromosomes 5, 6, 9, 11, 12, and 13. We compared BXSB/ll to >20 strains including the BXSB parental SB/Le and C57BL/6 strains. This revealed that BXSB/ll is a separate recombinant inbred line derived from SB/Le and C57BL/6, but distinctly different from BXSB, that most likely arose due to residual heterozygosity in the BXSB stock. Despite the continued presence of the powerful disease-susceptibility locus Bxs3, BXSB/ll mice do not develop disease. We propose that the disappearance of the disease phenotype in the BXSB/ll mice is due to the inheritance of one or more suppressor loci in the differentially inherited intervals between the BXSB/ll and BXSB strains.
Keywords AnimalsBreedingChromosomes/*genetics/immunologyGenetic Predisposition to DiseaseImmunity, Innate/*geneticsLupus Erythematosus, Systemic/genetics/immunologyMiceMice, Inbred StrainsPolymorphism, Single NucleotideQuantitative Trait Loci/*genetics/immunologyRecombination, Genetic/immunologySpecies Specificity
PMID: 17675504
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HAYWOOD, M. E. et al. BXSB/long-lived is a recombinant inbred strain containing powerful disease suppressor loci. In: Journal of Immunology, 2007, vol. 179, n° 4, p. 2428-2434.

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Deposited on : 2010-08-27

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