Polygenic control of susceptibility to murine systemic lupus erythematosus

Immunity. 1994 Jun;1(3):219-29. doi: 10.1016/1074-7613(94)90100-7.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / biosynthesis
  • Base Sequence
  • Chromosome Mapping
  • Crosses, Genetic
  • DNA Primers / genetics
  • Female
  • Genetic Linkage
  • Genetic Markers
  • H-2 Antigens / genetics
  • Heterozygote
  • Humans
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Nephritis / genetics
  • Lupus Nephritis / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Phenotype

Substances

  • Antibodies, Antinuclear
  • DNA Primers
  • Genetic Markers
  • H-2 Antigens