Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Strain BXSB/Mp mice develop a spontaneous lupus-like syndrome which is strikingly accelerated in males. The accelerated autoimmune disease occurs in male F1 hybrids with strains NZB/BINJ, SJL/J, and C57BL/6J when the male parent is BXSB but not in the reciprocal hybrid male nor in females. The pattern is similar in F2 hybrids with strains NZB and SJL. The accelerated disease in males occurs only when the Y chromosome is derived from recombinant inbred strain BXSB and ultimately from strain SB/Le.
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PMID:A Y chromosome associated factor in strain BXSB producing accelerated autoimmunity and lymphoproliferation. 31 77

The accelerated development of lupus-like autoimmune disease in male BXSB mice (H-2b, I-E-) is associated to the presence of a mutant gene, designated Yaa, located on their Y chromosome. To investigate whether the H-2b haplotype and/or the lack of expression of I-E molecules play any role in the Yaa-linked acceleration of autoimmune disease, an I-E+ BXSB.H-2d congenic strain was created by backcross procedures. We compared the development of autoimmune disease in the novel BXSB.H-2d (I-E+) strain to that of BXSB.H-2b (I-E-) and BXSB.H-2b/d (I-E+) heterozygous mice. Male BXSB.H-2d (I-E+) mice exhibited only a limited production of autoantibodies and a lower incidence of glomerulonephritis with a markedly prolonged survival rate, which were essentially identical to those of female BXSB mice of both-H-2b and H-2d haplotypes. However, BXSB.H-2b/d (I-E+) heterozygous males developed an accelerated disease comparable to that of conventional BXSB.H-2b (I-E-) male mice. These results indicate that the expression of I-E molecules and consequent clonal deletion or anergy of I-E reactive T cells does not appear to be responsible for the prevention of accelerated autoimmune disease in BXSB.H-2d (I-E+) male mice. The finding that the Yaa gene-induced acceleration of lupus-like autoimmune disease is modulated by gene(s) within or closely linked to the H-2 complex underlines the crucial role of the major histocompatibility complex and the polygenetic nature of autoimmune disease in BXSB mice.
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PMID:H-2-linked control of the Yaa gene-induced acceleration of lupus-like autoimmune disease in BXSB mice. 153 72

The Yaa gene (Y chromosome-linked autoimmune acceleration), linked to the BXSB/MpJ Y chromosome, and the autosomal recessive lpr (lymphoproliferation) gene have been shown to accelerate the progression of the lupus-like autoimmune syndrome in the BXSB and MRL strains, respectively. To compare more directly the role of the Yaa and lpr genes in the development of the autoimmune syndrome, the Y chromosome of BXSB mice was transferred to MRL mice by backcross procedures, and the effect of the Yaa gene on the autoantibody formation and the development of lupus-like nephritis in MRL mice was investigated in comparison with those bearing the lpr mutation. The Yaa gene as well as the lpr gene were able to shorten the life span of MRL mice as a result of the accelerated development of lethal lupus-like nephritis. However, the acceleration promoted by the Yaa gene (50% mortality rate: 12 months) was less severe than that induced by the lpr gene (50% mortality rate: 7 months). This may be related to the finding that the lpr gene enhanced the production of a large spectrum of autoantibodies, including anti-DNA, rheumatoid factors and anti-gp70, and of cryoglobulins, whereas only anti-gp70 production among the autoantibodies studies was markedly enhanced by the Yaa gene. The selective autoimmune accelerating effect of the Yaa gene was similarly observed in (NZW X MRL)F1 hybrid mice. Our results suggest that the Yaa gene, unlike the lpr gene, exhibits selective autoimmune accelerating activity, but as a result of increased formation of certain nephritogenic autoantibodies such as anti-gp70 antibodies, the Yaa gene is able to accelerate the progression of lupus-like nephritis in lupus-prone mice.
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PMID:Differential effect of the autoimmune Yaa and lpr genes on the acceleration of lupus-like syndrome in MRL/MpJ mice. 259 2

BXSB mice, a recently developed autoimmune strain, develop a human lupus-like disease with B cell hyperplasia in peripheral lymphoid organs. Unlike other experimental models of autoimmunity and human lupus, BXSB male mice manifest accelerated autoimmune phenomena through the influence of a Y chromosome-linked enhancing factor. The present studies were performed to investigate the features of B lymphopoiesis in BXSB mice and to determine whether differences exist between BXSB males and females in this respect. B lineage cell populations in the marrow of BXSB mice were identified phenotypically by studying the cytoplasmic mu-heavy chains of IgM (c mu), and functionally by their ability to acquire clonability and sIg in short-term liquid cultures. Male BXSB mice became deficient in both the precursors of functional B cells and c mu + pre-B cells by the age of 8 to 12 wk. This followed a transient increase in this population, which peaked when the mice were 2 to 4 wk old. In females, substantial numbers of functional B cell precursors and c mu + cells were maintained until more than 4 mo of age. Cells lacking Ig but bearing a B lineage cell antigen (14.8) were elevated in numbers in both BXSB males and females until 16 wk of age when compared to normal strains of mice. At the time pre-B cells and functional B precursors were elevated in numbers, some sIg- cells were shown to form colonies in mitogen-stimulated semisolid agar cultures without a period of preculture. Most of these sIg- cells seemed to bear the B lineage cell antigen (14.8). They were independent of both G-10 adherent regulatory cells and Thy-1+ cells for their colony formation. These results indicate that B lymphocyte formation may be maintained in a hyperactive state in BXSB females, whereas males become deficient in B cell precursors very early in life. This early decline might be related to the accelerated development of autoimmune disease in BXSB mice. Bone marrow transplantation studies showed that these unusual characteristics of B lymphopoiesis were reciprocally transferable with unseparated bone marrow cells between BXSB males and females. This finding indicates that sex hormones are not a critical variable in abnormal B lymphocyte formation in this strain, and that the premature deficiency of immediate B precursors in males may be regulated by a genetic factor(s) located on the Y chromosome.
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PMID:Age-dependent changes in B lymphocyte lineage cell populations of autoimmune-prone BXSB mice. 285 30

Stem cell activity in murine lupus was investigated by analyzing endogenous splenic colony-forming units in sublethally irradiated inbred, congenic, and consomic mice as well as F1 crosses. Splenic colony-forming units (CFU-s) were elevated (greater than 100) in young NZB mice as compared with nonautoimmune-prone mice (less than 10). In lpr/lpr and gld/gld mice, elevated levels of CFU-s were in association with disease manifestations. F1 crosses of inbred lpr/lpr mice often showed an excess of CFU-s in females when compared with male littermates. The autoimmunity accelerating factor on the Y chromosome of BXSB mice led to high numbers of CFU-s relative to female littermates. The xid gene, which does not alter stem cell activity but, instead, interferes with terminal lymphocyte maturation, had no effect on CFU-s in congenic mice. These studies demonstrate that there is a strong association between increased numbers of CFU-s and the development of generalized autoimmunity; increased stem cell division may be important for the development of murine lupus.
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PMID:The role of splenic colony-forming units in autoimmune disease. 313 59

The Y chromosome of the BXSB mouse has been shown to be responsible for the acceleration of lupus-like autoimmune syndrome in inbred BXSB mice and in their F1 hybrids with NZB or NZW mice. To further define the role of this as yet unidentified gene linked to the BXSB Y chromosome, designated Yaa (Y chromosome-linked autoimmune acceleration), the Y chromosome was transferred from the BXSB strain to nonautoimmune C57BL/6 (B6) mice. The effect of the Yaa gene on the autoantibody formation and the development of glomerulonephritis was investigated in B6 mice and in their F1 hybrids with NZW mice. The presence of the BXSB Y chromosome was not able to induce significant autoimmune responses in B6 mice. However, (NZW x B6)F1 males bearing the BXSB Y chromosome developed a severe lupus-like autoimmune syndrome, as documented by the production of anti-DNA antibodies and gp70-anti-gp70 immune complexes and the development of lethal lupus nephritis. Both sexes of (NZW x B6)F1 hybrids without the BXSB Y chromosome were essentially normal. Our results suggest that (a) the BXSB Y chromosome by itself is not sufficient to initiate autoimmune responses in nonautoimmune B6 mice, and (b) it is able to induce autoimmune responses in mice potentially capable of developing the disease, but whose autosomal abnormality by itself is not sufficient to develop autoimmune diseases.
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PMID:The Y chromosome from autoimmune BXSB/MpJ mice induces a lupus-like syndrome in (NZW x C57BL/6)F1 male mice, but not in C57BL/6 male mice. 326 Jan 84

BXSB mice represent a model for systemic lupus erythematosus (SLE). Due to a Y chromosome-linked genetic defect, males of this strain suffer from SLE much earlier in life than do the females. Comparative study of male and female BXSB mice therefore provides a way to identify abnormalities of the immune system leading to accelerated SLE development. The present work is part of an effort to examine whether T-cell alterations accompany such immune abnormalities. We focused on the evolution of Lyt-2+ T-cell subsets as defined by the 9F3 monoclonal antibody (MAb). By means of two-color flow cytofluorometry analysis, 9F3+ Lyt-2+ and 9F3- Lyt-2+ cell subsets could be clearly distinguished in the lymph nodes (LN) of BXSB mice. At as early as 2 months of age, BXSB males showed an increase of 9F3+ Lyt-2+ cell frequency compared to the females. This sex-related difference became more pronounced upon further aging. In 9- to 11-month-old mice, 9F3+ cells accounted for 80-85% of the LN Lyt-2+ population in the males versus 40-45% in the females. This difference reflected the selective expansion of 9F3+ Lyt-2+ cells in the males. It was also observed at a younger age in autoimmune (NZW X BXSB)F1 hybrids but not in old nonautoimmune C57Bl/6 or (CBA/N X BXSB)F1 mice. Moreover, adult thymectomy of BXSB mice was found to hasten the shift of 9F3-defined Lyt-2+ subset proportions. We postulate that the early imbalance of 9F3-defined Lyt-2+ subsets seen spontaneously in BXSB males may result from some thymus dysfunction and may be related to the development of autoimmunity.
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PMID:Alterations of the T-cell population in BXSB mice: early imbalance of 9F3-defined Lyt-2+ subsets occurs in the males with rapid onset lupic syndrome. 348 21

Previous studies have demonstrated that the Y chromosome of the BXSB mouse can lead to accelerated autoimmunity in inbred BXSB mice and in F1 hybrids. To additionally study the effects of the BXSB-Y, we have studied three sets of Y-consomic mice, NZB.BXSB-Y, NZW.BXSB-Y, and CBA/J.BXSB-Y, each consisting of background genes from the non-BXSB parent and the Y chromosome from the BXSB mouse. The effect of the BXSB-Y on autoantibody production, immunopathology, and survival was assessed. We found that the CBA/J.BXSB-Y mice showed few differences from control CBA/J males. In contrast, NZW.BXSB-Y males had accelerated renal and cardiac disease and early death, resembling that previously reported for (NZW X BXSB)F1 mice. NZB.BXSB-Y males had accelerated anti-erythrocyte autoantibodies but not accelerated anti-DNA. They lived almost as long as NZB mice. The presence of the BXSB-Y in all of the consomic mice was confirmed by crossing the consomic mice with BXSB females and demonstrating accelerated disease in the male offspring. This study demonstrates that the BXSB-Y chromosome autoimmune accelerating factor does not act alone but operates through other genes, and that the effects on different genetic backgrounds are different. The studies have implications for human lupus; they also provide a basis for future molecular biology studies of the BXSB-Y and the genes upon which it acts.
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PMID:Studies of consomic mice bearing the Y chromosome of the BXSB mouse. 398 99

Four different SLE-prone mice, NZB, (NZB x NZW)F1, MRL/MpJ-lpr/lpr, and male BXSB/MpJ, resisted the induction of tolerance to human IgG (HGG) at 5 wk, but not before 3 wk of age. However, female F1 hybrids between NZW and BXSB mice were easily made tolerant to HGG, although they develop an acute form of typical SLE similar to that seen in (NZB x NZW)F1 hybrid females. In addition, C57BL/6 mice bearing a mutant gene, lpr (lymphoproliferation), which produced significant amounts of various autoantibodies characteristic of murine SLE, were still as susceptible to tolerance induction as control C57BL/6 mice. In contrast, both (NZW x BXSB)F1 and (C3H x BXSB)F1 hybrid males carrying the abnormal Y chromosome of BXSB mice failed to become tolerant to HGG, although the extent of resistance to tolerance induction was less significant in (C3H x BXSB)F1 males than in (NZW x BXSB)F1 males. Our results suggest that 1) the defect in tolerance induction to heterologous IgG such as HGG is not necessarily required for the development of an SLE-like syndrome in mice; 2) the induction or enhanced production of autoantibodies by the lpr gene is not related to this cellular abnormality; but 3) a Y chromosome-associated factor from BXSB mice plays a significant role in the abnormality to resist tolerance induction as well as the acceleration of SLE. Our observations are consistent with the hypothesis that SLE may be based on highly specific abnormalities of immune responses to particular autoantigens, but not on a generalized breakdown of a tolerance mechanism.
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PMID:Resistance to tolerance induction is not prerequisite to development of murine SLE. 649 Dec 80

Both sexes of the F1 hybrids between SB/Le and NZW mice developed a spontaneous lupus-like disease. Their disease is essentially identical in time course and nature with autoimmune responses that are seen in the F1 hybrids between BXSB and NZW mice. The presence of abnormal Y chromosomes in the SB/Le strain was proved by the finding that the accelerated disease occurred in the F1 hybrid males only when the male parent was SB/Le but not NZW. The acceleration of disease in male F1 hybrids with abnormal Y chromosome was significantly associated with the enhanced formation of gp70 IC but not anti-DNA antibodies. These results indicate that all or almost all of the genetic abnormalities expressed in the BXSB strain are contributed by the SB/Le strain, and the Y chromosome-associated factor enhances the autoimmune response to serum gp70 antigen more markedly than to DNA antigens.
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PMID:Acute SLE in F1 hybrids between SB/Le and NZW mice; prominently enhanced formation of gp70 immune complexes by a Y chromosome-associated factor from SB/Le mice. 669 Jun 14


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