H-2-Linked regulation of serum gp70 production in mice

Maruyama, Naoki; Lindstrom, Cary O.

doi:10.1007/bf00696874

Cited by 17 publications

(14 citation statements)

References 35 publications

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“…B6 mice are known to have a Gv1 allele that results in low expression. The NZB loci mapped in the current analysis are distinct from other previously mapped loci that affect retroviral expression such as Gv2 and Sgp2 located on the telomeric end of chromosome 7 and Sgp1 linked to the H2 locus on chromosome 17 (49,50). It seems likely that many of the genetic contributions to gp70 levels reflect old insertions of murine leukemia viruses into the mouse genome and that mutation has allowed the expression of the envelope gene without other viral genes (51).…”

Section: Discussionmentioning

confidence: 73%

Genetic Control of Glycoprotein 70 Autoantigen Production and Its Influence on Immune Complex Levels and Nephritis in Murine Lupus

Tucker¹,

Vyse

Rozzo

et al. 2000

The Journal of Immunology

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The F1 hybrids of New Zealand Black (NZB) and New Zealand White (NZW) mice spontaneously develop an autoimmune disease that serves as a model for human systemic lupus erythematosus. Autoimmunity in (NZB × NZW)F1 mice includes the production of autoantibodies to the endogenous retroviral envelope glycoprotein, gp70, and gp70-anti-gp70 immune complexes (gp70 IC) have been implicated in the development of lupus nephritis in these animals. We used backcross and intercross combinations of C57BL/6 (B6; low gp70 levels) and NZB mice (high gp70 levels) to examine the contribution of serum gp70 Ag levels to the development of gp70 IC and nephritis. Analysis of (B6.H2z × NZB)F1 × NZB backcross mice and (NZB × B6)F2 mice showed a much stronger association of gp70 IC with kidney disease compared with IgG anti-chromatin autoantibodies in both populations of mice. Serum levels of gp70 correlated with production of gp70 IC in mice producing autoantibodies, although the overall effect on nephritis appeared to be small. Genetic mapping revealed three NZB-derived regions on chromosomes 2, 4, and 13 that were strongly linked with increased gp70 levels, and together, accounted for over 80% of the variance for this trait. However, additional linkage analyses of these crosses showed that loci controlling autoantibody production rather than gp70 levels were most important in the development of nephritogenic immune complexes. Together, these studies characterize a set of lupus-susceptibility loci distinct from those that control autoantibody production and provide new insight into the components involved in the strong association of gp70 IC with murine lupus nephritis.

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Section: Discussionmentioning

confidence: 73%

Genetic Control of Glycoprotein 70 Autoantigen Production and Its Influence on Immune Complex Levels and Nephritis in Murine Lupus

Tucker¹,

Vyse

Rozzo

et al. 2000

The Journal of Immunology

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“…A region on distal chromosome 4 was linked to serum gp70 levels in NZB mice on a C57BL/6 background (9), and linkage with serum gp70 and/or serum gp70IC levels has also been demonstrated on chromosome 7 in NZW and 129 mice on a C57BL/6 background (12,13). A number of other loci have demonstrated weak linkage to gp70 and gp70IC, including chromosome 17, at the H2 complex, in non-H2-matched cohorts (8,12,14).…”

mentioning

confidence: 99%

A Novel Locus Regulates Both Retroviral Glycoprotein 70 and Anti-Glycoprotein 70 Antibody Production in New Zealand Mice When Crossed with BALB/c

Rigby

Rozzo

Gill

et al. 2004

The Journal of Immunology

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Lupus-prone New Zealand Black and New Zealand White mice produce high serum levels of the endogenous retroviral envelope protein gp70 and develop an Ab response to this autoantigen as part of their autoimmune disease. Linkage analysis of two crosses involving New Zealand and BALB/c mice mapped these traits to a group of overlapping loci, including a novel locus on proximal chromosome 12. This locus was linked with serum gp70 and the autoimmune response against it. The linkage of serum gp70 levels to a previously described locus on distal chromosome 4 was also confirmed. Sequence analysis of a candidate gene on distal chromosome 4, Fv1, provided support that this gene may be associated with the control of serum gp70 levels in both New Zealand Black and New Zealand White mice. Linkage data and statistical analysis confirmed a close correlation between gp70 Ag and anti-gp70 Ab levels, and together gave support to the concept that a threshold level of gp70 is required for the production of anti-gp70 Abs. Serum levels of anti-gp70 Abs were closely correlated with the presence of renal disease, more so than anti-dsDNA Abs. Understanding the genetic basis of this complex autoantigen-autoantibody system will provide insight into the pathogenesis of lupus in mice, which may have implications for human disease.

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“…Concentrations of SU in sera were determined by using '"Ilabelled SU of Rauscher murine leukaemia virus to inhibit the binding of goat antibody to feline leukaemia virus as described previously [8].…”

Section: Radioimmunoassay For Sumentioning

confidence: 99%

“…The major site of serum SU synthesis is hepatocytes [7]. Since the production of serum SU is genetically determined, we have investigated some genetic features controlling SU production in hepatocytes [8,9]. The results of those experiments and others suggest that the production of SU in hepatocytes is restricted at the transcriptional level [10].…”

Section: Introductionmentioning

confidence: 99%

“…However, we found that LPS has a completely different effect on BIO.S mice. Although this strain shows normal induction of haptoglobin after LPS injection [8,10], the induction of serum SU is completely suppressed. Moreover, this suppression is complete, even in the hybrid offspring of crosses between BIO.S and NZB parents with high levels of serum SU.…”

Section: Introductionmentioning

confidence: 99%

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Induction of endogenous retroviral gene product (SU) as an acute-phase protein by IL-6 in murine hepatocytes

Itoh

Maruyama

Kitamura

et al. 1992

Clinical and Experimental Immunology

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SUMMARYThe efTect of Lps locus and IL-6 on the production of SU (previously termed gp70), a mouse endogenous retroviral gene product, was studied. Back-cross studies using the progeny between (NZB X C3H/HeJ)Fl and C3H/HeJ mice indicate that the basal level of SU is not associated with the Lps locus on chromosome 4. Lipopolysaccharide (LPS) mitogen response-negative mice did not show the enhancement of serum SU production after LPS injection. Spleen cells from LPS-mitogen response-positive but not from negative mice showed increase of IL-6 synthesis in the presence of LPS. Since IL-6 may be involved in the production of serum SU, we tested the effect of IL-6 in a primary hepatocyte culture system. SU production was clearly enhanced in the presence of recombinant IL-6, indicating that IL-6 induced by LPS can enhance the expression of retroviral genome.

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H-2-Linked regulation of serum gp70 production in mice

Cited by 17 publications

References 35 publications

Genetic Control of Glycoprotein 70 Autoantigen Production and Its Influence on Immune Complex Levels and Nephritis in Murine Lupus

Genetic Control of Glycoprotein 70 Autoantigen Production and Its Influence on Immune Complex Levels and Nephritis in Murine Lupus

A Novel Locus Regulates Both Retroviral Glycoprotein 70 and Anti-Glycoprotein 70 Antibody Production in New Zealand Mice When Crossed with BALB/c

Induction of endogenous retroviral gene product (SU) as an acute-phase protein by IL-6 in murine hepatocytes

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