Polygenic control of susceptibility to murine systemic lupus erythematosus.
Susceptibility to glomerulonephritis (GN) and anti-dsDNA autoantibody production was analyzed in crosses with a newly developed systemic lupus erythematosus-susceptible inbred strain, NZM/Aeg2410. The mode of inheritance and the number and location of systemic lupus erythematosus-associated susceptibility loci were analyzed by interval mapping in a backcross with C57BL/6. Three chromosomal intervals containing strong recessive GN susceptibility alleles were identified on chromosomes 1, 4, and 7, each containing several potentially interesting candidate genes. Heterozygosity at H-2 was also found to correlate strongly with GN susceptibility, consistent with previous findings in the NZB/NZW parental strain model. Logistic regression analysis indicated that each of these susceptibility alleles independently accounted for a component of GN susceptibility, and that susceptibility was inherited as a threshold genetic liability in this model system.
Morel
L
L
Center for Mammalian Genetics, College of Medicine, University of Florida, Gainesville 32610.
Rudofsky
U H
UH
Longmate
J A
JA
Schiffenbauer
J
J
Wakeland
E K
EK
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001483:Base Sequence; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D017931:DNA Primers / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006183:H-2 Antigens / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010641:Phenotype
D000974:Antibodies, Antinuclear; D017931:DNA Primers; D005819:Genetic Markers; D006183:H-2 Antigens