Genetic origin of lupus in NZB/SWR hybrids: Lessons from an intercross study

Shangkui Xie, Li Li, SoogHee Chang, Ruchi Sharma, Arunan Kaliyaperumal, Syamal K. Datta, Chandra Mohan

Research output: Contribution to journalArticle

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Abstract

Objective. (SWR x NZB)F1 (or SNF1) hybrid mice succumb to lupus nephritis. A previous analysis of SNF1 x NZB backcross mice revealed the existence of 4 SWR loci (H2 on chromosome 17, Swrl-1 on chromosome 1, Swrl-2 on chromosome 14, and Swrl-3 on chromosome 18) and 2 NZB loci (Nba1 and Lbw2/Sbw2, both on chromosome 4). A second study focusing on SNF1 x SWR backcross offspring uncovered 5 suggestive loci for antinuclear antibody formation, consisting of 3 dominant NZB contributions (Nba4 on chromosome 5, Lbw4 on chromosome 6, and Nba5 on chromosome 7) and 2 recessive SWR contributions (Swrl-1 on chromosome 1 and Swrl-4 on chromosome 10). The present intercross study was executed to replicate the earlier findings, using an independent panel of (SWR x NZB)F2 offspring. Methods. A panel of (NZB x SWR)F2 hybrids were phenotyped (for renal disease, early mortality, and a variety of autoantibodies) and genotyped (using 95 microsatellite primers positioned across all 19 autosomes and the X chromosome). Linkage analysis was conducted using the derived phenotype and genotype data, with the interval-mapping program MapManager. Results. Four suggestive loci were mapped: Swrl-5 on chromosome 1 (peak at 106 cM), linked to hypergammaglobulinemia; an NZB locus on chromosome 5 (Nba4; peak at 15 cM), linked to IgG anti-single-stranded DNA (anti-ssDNA) antibodies, IgG anti-doubled-stranded DNA (anti-dsDNA) antibodies, and glomerulonephritis; an NZB locus on chromosome 13 (Nba6; peak at 28 cM), linked to IgG anti-dsDNA antibodies; and an SWR locus on chromosome 14 (Swrl-2; peak at 30 cM), linked to IgG anti-ssDNA antibodies. Eight additional loci revealed linkage at P < 0.01, of which 7 co-mapped with lupus susceptibility loci previously identified in other models. Conclusion. Considering all 3 mapping studies together, lupus in SWR/NZB hybrids appears to be the epistatic end product of several distinct loci, of which 3 SWR-derived loci (Swrl-1, Swrl-2, and Swrl-3) and 5 NZB-derived loci (Nba1, Nba3, Nba4, Nba5, and Lbw4) have been independently confirmed. The immunologic functions and molecular identities of these loci await elucidation.

Original languageEnglish (US)
Pages (from-to)659-667
Number of pages9
JournalArthritis and Rheumatism
Volume52
Issue number2
DOIs
StatePublished - Feb 2005

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Chromosomes, Human, Pair 1
Chromosomes, Human, Pair 14
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 2
Antibodies
Inbred NZB Mouse
Hypergammaglobulinemia
Chromosomes, Human, Pair 18
Chromosomes, Human, Pair 13
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 4
Chromosomes, Human, Pair 6
Lupus Nephritis
Chromosomes, Human, Pair 7
Single-Stranded DNA
Antinuclear Antibodies
X Chromosome
Glomerulonephritis
Microsatellite Repeats

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Xie, S., Li, L., Chang, S., Sharma, R., Kaliyaperumal, A., Datta, S. K., & Mohan, C. (2005). Genetic origin of lupus in NZB/SWR hybrids: Lessons from an intercross study. Arthritis and Rheumatism, 52(2), 659-667. https://doi.org/10.1002/art.20786

Genetic origin of lupus in NZB/SWR hybrids : Lessons from an intercross study. / Xie, Shangkui; Li, Li; Chang, SoogHee; Sharma, Ruchi; Kaliyaperumal, Arunan; Datta, Syamal K.; Mohan, Chandra.

In: Arthritis and Rheumatism, Vol. 52, No. 2, 02.2005, p. 659-667.

Research output: Contribution to journalArticle

Xie, S, Li, L, Chang, S, Sharma, R, Kaliyaperumal, A, Datta, SK & Mohan, C 2005, 'Genetic origin of lupus in NZB/SWR hybrids: Lessons from an intercross study', Arthritis and Rheumatism, vol. 52, no. 2, pp. 659-667. https://doi.org/10.1002/art.20786
Xie S, Li L, Chang S, Sharma R, Kaliyaperumal A, Datta SK et al. Genetic origin of lupus in NZB/SWR hybrids: Lessons from an intercross study. Arthritis and Rheumatism. 2005 Feb;52(2):659-667. https://doi.org/10.1002/art.20786
Xie, Shangkui ; Li, Li ; Chang, SoogHee ; Sharma, Ruchi ; Kaliyaperumal, Arunan ; Datta, Syamal K. ; Mohan, Chandra. / Genetic origin of lupus in NZB/SWR hybrids : Lessons from an intercross study. In: Arthritis and Rheumatism. 2005 ; Vol. 52, No. 2. pp. 659-667.
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abstract = "Objective. (SWR x NZB)F1 (or SNF1) hybrid mice succumb to lupus nephritis. A previous analysis of SNF1 x NZB backcross mice revealed the existence of 4 SWR loci (H2 on chromosome 17, Swrl-1 on chromosome 1, Swrl-2 on chromosome 14, and Swrl-3 on chromosome 18) and 2 NZB loci (Nba1 and Lbw2/Sbw2, both on chromosome 4). A second study focusing on SNF1 x SWR backcross offspring uncovered 5 suggestive loci for antinuclear antibody formation, consisting of 3 dominant NZB contributions (Nba4 on chromosome 5, Lbw4 on chromosome 6, and Nba5 on chromosome 7) and 2 recessive SWR contributions (Swrl-1 on chromosome 1 and Swrl-4 on chromosome 10). The present intercross study was executed to replicate the earlier findings, using an independent panel of (SWR x NZB)F2 offspring. Methods. A panel of (NZB x SWR)F2 hybrids were phenotyped (for renal disease, early mortality, and a variety of autoantibodies) and genotyped (using 95 microsatellite primers positioned across all 19 autosomes and the X chromosome). Linkage analysis was conducted using the derived phenotype and genotype data, with the interval-mapping program MapManager. Results. Four suggestive loci were mapped: Swrl-5 on chromosome 1 (peak at 106 cM), linked to hypergammaglobulinemia; an NZB locus on chromosome 5 (Nba4; peak at 15 cM), linked to IgG anti-single-stranded DNA (anti-ssDNA) antibodies, IgG anti-doubled-stranded DNA (anti-dsDNA) antibodies, and glomerulonephritis; an NZB locus on chromosome 13 (Nba6; peak at 28 cM), linked to IgG anti-dsDNA antibodies; and an SWR locus on chromosome 14 (Swrl-2; peak at 30 cM), linked to IgG anti-ssDNA antibodies. Eight additional loci revealed linkage at P < 0.01, of which 7 co-mapped with lupus susceptibility loci previously identified in other models. Conclusion. Considering all 3 mapping studies together, lupus in SWR/NZB hybrids appears to be the epistatic end product of several distinct loci, of which 3 SWR-derived loci (Swrl-1, Swrl-2, and Swrl-3) and 5 NZB-derived loci (Nba1, Nba3, Nba4, Nba5, and Lbw4) have been independently confirmed. The immunologic functions and molecular identities of these loci await elucidation.",
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AU - Kaliyaperumal, Arunan

AU - Datta, Syamal K.

AU - Mohan, Chandra

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N2 - Objective. (SWR x NZB)F1 (or SNF1) hybrid mice succumb to lupus nephritis. A previous analysis of SNF1 x NZB backcross mice revealed the existence of 4 SWR loci (H2 on chromosome 17, Swrl-1 on chromosome 1, Swrl-2 on chromosome 14, and Swrl-3 on chromosome 18) and 2 NZB loci (Nba1 and Lbw2/Sbw2, both on chromosome 4). A second study focusing on SNF1 x SWR backcross offspring uncovered 5 suggestive loci for antinuclear antibody formation, consisting of 3 dominant NZB contributions (Nba4 on chromosome 5, Lbw4 on chromosome 6, and Nba5 on chromosome 7) and 2 recessive SWR contributions (Swrl-1 on chromosome 1 and Swrl-4 on chromosome 10). The present intercross study was executed to replicate the earlier findings, using an independent panel of (SWR x NZB)F2 offspring. Methods. A panel of (NZB x SWR)F2 hybrids were phenotyped (for renal disease, early mortality, and a variety of autoantibodies) and genotyped (using 95 microsatellite primers positioned across all 19 autosomes and the X chromosome). Linkage analysis was conducted using the derived phenotype and genotype data, with the interval-mapping program MapManager. Results. Four suggestive loci were mapped: Swrl-5 on chromosome 1 (peak at 106 cM), linked to hypergammaglobulinemia; an NZB locus on chromosome 5 (Nba4; peak at 15 cM), linked to IgG anti-single-stranded DNA (anti-ssDNA) antibodies, IgG anti-doubled-stranded DNA (anti-dsDNA) antibodies, and glomerulonephritis; an NZB locus on chromosome 13 (Nba6; peak at 28 cM), linked to IgG anti-dsDNA antibodies; and an SWR locus on chromosome 14 (Swrl-2; peak at 30 cM), linked to IgG anti-ssDNA antibodies. Eight additional loci revealed linkage at P < 0.01, of which 7 co-mapped with lupus susceptibility loci previously identified in other models. Conclusion. Considering all 3 mapping studies together, lupus in SWR/NZB hybrids appears to be the epistatic end product of several distinct loci, of which 3 SWR-derived loci (Swrl-1, Swrl-2, and Swrl-3) and 5 NZB-derived loci (Nba1, Nba3, Nba4, Nba5, and Lbw4) have been independently confirmed. The immunologic functions and molecular identities of these loci await elucidation.

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