BXSB/long-lived is a recombinant inbred strain containing powerful disease suppressor loci.
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.
Haywood
Michelle E K
ME
Rheumatology Section, Imperial College, London, United Kingdom.
Gabriel
Luisa
L
Rose
S Jane
SJ
Rogers
Nicola J
NJ
Izui
Shozo
S
Morley
Bernard J
BJ
D000818:Animals; D001947:Breeding; D002875:Chromosomes / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics* / Q000276:immunology; D011995:Recombination, Genetic / Q000276:immunology; D013045:Species Specificity