Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. 1994 Oct 11; 91(21): 10168–10172.

Lupus susceptibility loci in New Zealand mice.


Susceptibility to systemic lupus erythematosus has been unequivocally established to be an inherited trait, but the exact genes and how they confer susceptibility remain largely unknown. In this study of (NZB x NZW)F2 intercross mice, we used linkage analysis of markers covering > 90% of the autosomal genome and identified eight susceptibility loci (Lbw1 to -8, chromosomes 17, 4-7, 18, 1, 11, respectively) associated with antichromatin autoantibody production, glomerulonephritis, and/or mortality. Only one locus, the major histocompatibility complex, was linked to all three traits. Two other loci were associated with both glomerulonephritis and mortality, whereas the remaining loci were linked to one of the above traits. Two additional loci (Sbw1 and -2) that contributed to splenomegaly were also identified. The Sbw2 locus mapped to the identical region as Lbw2, a locus on chromosome 4 linked to glomerulonephritis and mortality, suggesting a single locus with pleiotropic effects. The results indicate that the immunopathologic features of lupus are affected by distinct, but additive, genetic contributions. Studies to determine the nature of the genes associated with these loci should help define the genetic mechanisms involved in this systemic autoimmune disease.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Knight JG, Adams DD. Three genes for lupus nephritis in NZB x NZW mice. J Exp Med. 1978 Jun 1;147(6):1653–1660. [PMC free article] [PubMed]
  • Hirose S, Ueda G, Noguchi K, Okada T, Sekigawa I, Sato H, Shirai T. Requirement of H-2 heterozygosity for autoimmunity in (NZB X NZW)F1 hybrid mice. Eur J Immunol. 1986 Dec;16(12):1631–1633. [PubMed]
  • Kotzin BL, Palmer E. The contribution of NZW genes to lupus-like disease in (NZB x NZW)F1 mice. J Exp Med. 1987 May 1;165(5):1237–1251. [PMC free article] [PubMed]
  • Ghosh S, Palmer SM, Rodrigues NR, Cordell HJ, Hearne CM, Cornall RJ, Prins JB, McShane P, Lathrop GM, Peterson LB, et al. Polygenic control of autoimmune diabetes in nonobese diabetic mice. Nat Genet. 1993 Aug;4(4):404–409. [PubMed]
  • Dietrich W, Katz H, Lincoln SE, Shin HS, Friedman J, Dracopoli NC, Lander ES. A genetic map of the mouse suitable for typing intraspecific crosses. Genetics. 1992 Jun;131(2):423–447. [PMC free article] [PubMed]
  • Andrews BS, Eisenberg RA, Theofilopoulos AN, Izui S, Wilson CB, McConahey PJ, Murphy ED, Roths JB, Dixon FJ. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978 Nov 1;148(5):1198–1215. [PMC free article] [PubMed]
  • Burlingame RW, Rubin RL, Balderas RS, Theofilopoulos AN. Genesis and evolution of antichromatin autoantibodies in murine lupus implicates T-dependent immunization with self antigen. J Clin Invest. 1993 Apr;91(4):1687–1696. [PMC free article] [PubMed]
  • Lander ES, Green P, Abrahamson J, Barlow A, Daly MJ, Lincoln SE, Newberg LA, Newburg L. MAPMAKER: an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations. Genomics. 1987 Oct;1(2):174–181. [PubMed]
  • Jacob HJ, Pettersson A, Wilson D, Mao Y, Lernmark A, Lander ES. Genetic dissection of autoimmune type I diabetes in the BB rat. Nat Genet. 1992 Sep;2(1):56–60. [PubMed]
  • Watson ML, Rao JK, Gilkeson GS, Ruiz P, Eicher EM, Pisetsky DS, Matsuzawa A, Rochelle JM, Seldin MF. Genetic analysis of MRL-lpr mice: relationship of the Fas apoptosis gene to disease manifestations and renal disease-modifying loci. J Exp Med. 1992 Dec 1;176(6):1645–1656. [PMC free article] [PubMed]
  • Klinman DM. Polyclonal B cell activation in lupus-prone mice precedes and predicts the development of autoimmune disease. J Clin Invest. 1990 Oct;86(4):1249–1254. [PMC free article] [PubMed]
  • Prud'homme GJ, Balderas RS, Dixon FJ, Theofilopoulos AN. B cell dependence on and response to accessory signals in murine lupus strains. J Exp Med. 1983 Jun 1;157(6):1815–1827. [PMC free article] [PubMed]
  • Raveche ES, Novotny EA, Hansen CT, Tjio JH, Steinberg AD. Genetic studies in NZB mice. V. Recombinant inbred lines demonstrate that separate genes control autoimmune phenotype. J Exp Med. 1981 May 1;153(5):1187–1197. [PMC free article] [PubMed]
  • Risch N, Ghosh S, Todd JA. Statistical evaluation of multiple-locus linkage data in experimental species and its relevance to human studies: application to nonobese diabetic (NOD) mouse and human insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 1993 Sep;53(3):702–714. [PMC free article] [PubMed]
  • Hirose S, Tokushige K, Kinoshita K, Nozawa S, Saito J, Nishimura H, Shirai T. Contribution of the gene linked to the T cell receptor beta chain gene complex of NZW mice to the autoimmunity of (NZB x NZW)F1 mice. Eur J Immunol. 1991 Mar;21(3):823–826. [PubMed]
  • Hirose S, Sekigawa I, Ozaki S, Sato H, Shirai T. Genetic regulation of hypergammaglobulinaemia and the correlation to autoimmune traits in (NZB X NZW) F1 hybrid. Clin Exp Immunol. 1984 Dec;58(3):694–702. [PMC free article] [PubMed]
  • Drake CG, Babcock SK, Palmer E, Kotzin BL. Genetic analysis of the NZB contribution to lupus-like autoimmune disease in (NZB x NZW)F1 mice. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4062–4066. [PMC free article] [PubMed]
  • Linsley PS, Ledbetter JA. The role of the CD28 receptor during T cell responses to antigen. Annu Rev Immunol. 1993;11:191–212. [PubMed]
  • Strasser A, Whittingham S, Vaux DL, Bath ML, Adams JM, Cory S, Harris AW. Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8661–8665. [PMC free article] [PubMed]
  • Sidman CL, Marshall JD, Beamer WG, Nadeau JH, Unanue ER. Two loci affecting B cell responses to B cell maturation factors. J Exp Med. 1986 Jan 1;163(1):116–128. [PMC free article] [PubMed]
  • Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y, Miyata T, Taniguchi T. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell. 1988 Sep 9;54(6):903–913. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Gene
    Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
  • GEO Profiles
    GEO Profiles
    Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
  • HomoloGene
    HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...