Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune New Zealand white (NZW) mice contribute to (New Zealand black x New Zealand white)F1 mice 1 or more major histocompatibility complex-linked genes that strongly correlate with susceptibility to murine lupus. The NZW class II major histocompatibility complex genes, I-E alpha and I-E beta, were cloned and sequenced and found to differ from normal B10.PL (H-2u) mice by 3 amino acids in the first domain of the I-E beta subunit. Of these differences, the arginine at position 72 of NZW mice could be an important disease determinant since it lies in a predicted antigen-binding cleft.
 ...
PMID:Sequence of I-E genes from autoimmune New Zealand white mice. 210 15

These experiments examined the effects of genes outside of the H-2 region on disease susceptibility and pathogenesis. Four strains of mice with the susceptible H-2 type, H-2d, but different non-H-2 genes were studied. B10, D2, Balb/c, NZB, and DBA/2J mice were injected with 4 mg of apoferritin i.p. q.d. for 28 days. B10, D2 and Balb/c mice developed proliferative and crescentic glomerulonephritis. NZB mice developed proliferative and crescentic glomerulonephritis with wire loop lesions suggestive of lupus. DBA/2J mice developed only minimal mesangial proliferation without crescents or necrosis. Electron microscopy showed subepithelial and mesangial deposits in B10, D2, moderate subepithelial and mesangial deposits in Balb/c, and marked mesangial, subendothelial and subepithelial deposits in NZB. Immunofluorescence demonstrated the presence of IgG, IgM, C3 and apoferritin in these deposits. The DBA/2J mice had only minimal mesangial deposits by immunofluorescence and electron microscopy. These experiments demonstrate that non-H-2 genes alter the H-2d determined disease susceptibility seen in H-2 congenic mice. NZB genes can alter the disease so that lupus-like lesions develop and DBA/2J genes can substantially ameliorate the disease.
 ...
PMID:Non-H-2 genes alter the H-2 determined susceptibilities in immune complex nephritis. 253 Mar 82

Groups of nonirradiated BDF1 mice were injected with unseparated spleen cells from B10, B10.D2, or DBA/2 donors. The diverse clinical and pathologic symptoms that developed during the course of the ensuing graft-vs-host reaction (GVHR) were related to the functional subsets of donor-T cells activated in the host. The activation of F1-specific donor T suppressor (TS) cells was confined to those GVH F1 mice that developed acute GVH disease (GVHD) (donor B10 or B10.D2). Moreover, activation in these GVH F1 mice of the Lyt-1-2+ donor TS cells sharply preceded the onset of and coincided with (week 2 to 6) the suppressive pathologic symptoms characteristic of acute GVHD, such as pancytopenia and suppression of splenic IgG production. The activation of these alloreactive TS effector cells was briefly preceded by the activation of F1-specific Lyt-1+-2- donor T helper (TH) cells and stimulation of the host's lymphoid tissue. Thus, in acute GVHD, a sequential alloactivation first of donor TH and then of TS cells was found. Those F1 mice that recovered from acute GVHD and developed stimulatory pathologic symptoms showed a concomitant loss of donor TS cell activity. An initial activation of F1-specific Lyt-1 +2- donor TH cells was also found in that parent----F1 combination (donor DBA/2), which failed to develop acute GVHD. Significantly in that combination, the alloactivation of donor TH cells was not followed by activation of significant numbers of donor TS cells. Instead, the DBA/2-injected BDF1 mice directly developed a persistent increase in splenic Ig formation and lupus-like GVHD.
 ...
PMID:Allosuppressor- and allohelper-T cells in acute and chronic graft-vs-host disease. IV. Activation of donor allosuppressor cells is confined to acute GVHD. 623 Mar 90

Lupus-prone (NZB X NZW)F1 (B X W) mice and MRL-lpr and BXSB mice were examined for the prevalence of hypertension and levels of plasma renin activity (PRA). Hypertension (greater than 145 mmHg) was observed only in female and male B X W mice with severe nephritis; in female MRL-lpr and male BXSB mice severe nephritis developed without blood pressure elevation (80-135 mmHg). The B X W parental strains, NZB and NZW, and the MRL-lpr congenic partners, MRL- +, did not become hypertensive as they aged. Other strains of mice, aged 3-32 months (A/HeN, BALB/cJ, BALB/cByJ, B10.S/Sg, B10.D2/ oSn , CBA/J, C3H/HeJ, SJL/J and [SJL X NZW]F1), also had normal blood pressure (98-122 mmHg). All mice with lupus nephritis had low PRA, even those with hypertension; furthermore, the MRL-lpr strain had low or undetectable PRA (2 +/- 1 ng/ml/hr), even when kidneys were normal. NZB, NZW, and MRL- + mice had normal PRA (10-16 ng/ml/hr). Thus, B X W mice frequently developed low renin hypertension during the last phase of their renal disease; whereas MRL-lpr and BXSB mice died from renal disease without observable increases in blood pressure.
 ...
PMID:Differences in the occurrence of hypertension among (NZB X NZW)F1, MRL-lpr, and BXSB mice with lupus nephritis. 637 6

We compared the findings in the wasting syndrome seen in [MRL lpr/lpr--> MRL +/+] chimeras with those of chronic graft versus host disease (GVHD) in [B10.D2-->BALB/c] chimeras. BALB/c mice were lethally irradiated and administered B10.D2 spleen and bone marrow cells. These mice are identical to MHC and Mls but differ as to genetic background. As a result of chronic GVHD, these [B10.D2-->BALB/c] chimeras showed hair loss, weight loss and atrophy of lymph nodes and spleen beginning 5 weeks after the transplantation. MRL lpr/lpr mice carry the lpr gene and spontaneously develop generalized lymph node swelling and lupus-like autoimmune disease, while congenic MRL +/+ mice lack the lpr gene. The [MRL lpr/lpr-->MRL +/+] chimeras showed wasting and the same symptoms as in [B10.D2-BALB/c] chimeras beginning 16 weeks after cell transfer. Skin biopsy from both chimeras showed very similar changes on HE staining and on immunoperoxidase staining for Ia and Thy-1. Our data suggest that very small differences in minor histocompatibility may induce GVHD which produces severe wasting with lethal consequences. Finally, we succeeded in transferring the wasting syndrome seen in the [MRL lpr/lpr--> MRL +/+] chimera to other MRL +/+ mice by transplanting spleen cells from the [MRL lpr/lpr-->MRL +/+] chimera to lethally irradiated MRL +/+ mice.
 ...
PMID:Comparison of wasting syndrome in [MRL lpr/lpr-->MRL +/+] chimera and graft versus host disease in [B10.D2-->BALB/c] chimera and an attempt to transfer the wasting syndrome in [MRL lpr/lpr-->MRL +/+] to MRL +/+ mice. 791 43

The Y-linked autoimmune accelerating gene mutation (yaa), first discovered in the BXSB mouse strain, is known to accelerate spontaneous autoantibody production and subsequent development of lupus disease. We have investigated the role of the yaa gene in the development of the type II collagen (CII)-induced arthritis (CIA), which is used as a model for rheumatoid arthritis. In contrast to the accelerating effects on development of lupus autoimmunity we can show that the presence of BXSB Y chromosome carrying the yaa gene block development of CIA in F1 crosses with three normally CIA-susceptible strains, DBA/1, C3H.Q and B10.Q. Backcross experiments showed an additional modulatory effect from other BXSB genes or possibly from DBA/1 X chromosome. To evaluate the effect mediated by the yaa gene alone, the BXSB Y chromosome was bred into the DBA/1 gene background. The DBA/1 congenic DBA/1.yaa male mice were less susceptible to arthritis development than their DBA/1 counterparts. (B10.QxDBA/1.yaa)F1 acquired resistance to arthritis development similar to that of DBA/1.yaa, indicating a role for the yaa gene alone. The serum levels of autoantibodies to CII were significantly suppressed in all strains carrying yaa. In DBA/1.yaa mice a reduced number of T cells were found to produce interferon-gamma after in vitro stimulation with CII. Thus, although autoreactive B cells are important in both diseases they play different roles in murine lupus and in CIA.
 ...
PMID:The Y chromosome-linked "autoimmune accelerating" yaa gene suppresses collagen-induced arthritis. 818 31

Irradiation with ultraviolet B (UVB; 290-320 nm) initiates systemic immunosuppression of contact hypersensitivity (CHS). UV dose-responses for suppression of CHS to trinitrochlorobenzene were established in 18 strains of inbred mice. Three phenotypes with significantly different susceptibilities to UV suppression were identified. The phenotypes were: high (HI) susceptibility, 50% suppression with 0.7-2.3 kJ/m2 UV (C57BL/6, C57BL/10, and C57L and NZB females); low (LO) susceptibility, 50% suppression with 9.6-12.3 kJ/m2 UV (BALB/c, AKR, SJL and NZW), and intermediate (INT) susceptibility, 50% suppression with 4.7-6.9 kJ/m2 UV (DBA/2, C57BR, C3H/HeJ, C3H/HeN, CBA/N and A/J). UV suppression was not correlated with skin pigmentation or with the magnitude of the CHS response in non-irradiated animals. Major histocompatibility complex (MHC) haplotype was not correlated with UV suppression in MHC congenic strains B10.D2/oSnJ, B10.D2/nSnJ, B10.BR/SgSnJ, and A.BY/SnJ. There were no sex differences in UV suppression in BALB/c, C57BL/6, or NZW animals. In the autoimmune NZB strain, however, male mice (LO) were seven times less sensitive to UV suppression than NZB female mice (HI). Both sexes of (NZB x NZW)F1 and (NZW x NZB)F1 mice were HI, supporting dominance of HI over LO. Thus there are genetic factors and interacting sex-limited factors determining susceptibility to UV suppression. These findings may be of relevance to UV-related diseases such as photosensitive lupus and skin cancer.
 ...
PMID:Susceptibility to immunosuppression by ultraviolet B radiation in the mouse. 822 36

Antibodies against the Sm antigen are characteristic of systemic lupus erythematosus (SLE). They are found in 20-30% of SLE patients and it has been shown previously that up to 70% of SLE sera react with synthetic fragments 1-20 and 44-67 of the Sm-D polypeptide. To determine whether injections of these peptides might be pathogenic both were administered intraperitoneally into normal mouse strains BALB/c (H-2d), B10/brown (H-2k) and C57BL/6 (H-2b) and an autoimmune strain MRL/lpr (H-2k). IgG antibodies against peptide 1-20 were detected by ELISA in the sera of BALB/c and MRL/lpr mice but not in the sera of B10/brown and C57BL/6 mice. IgG antibodies against peptide 44-67 were found in the sera of BALB/c, B10/brown and MRL/lpr mice but not in the sera of C57BL/6 mice. Neither fragment induced a response against the whole Sm-D antigen as detected by Western blotting. Reactivity to synthetic fragments from other nuclear antigens was however detected in the sera of MRL/lpr mice, especially in those mice injected with Sm-D peptide 44-67 emulsified in Freund's adjuvant. Following immunization with Sm-D peptides, antibodies to ssDNA or dsDNA were not detected in the sera of BALB/c, B10/brown and C57BL/6 mice and in the MRL/lpr mice the naturally occurring production of these antibodies was not enhanced. No difference in IgG deposition in the renal glomeruli of the mice injected with the peptides compared with the control groups was observed. These results suggest that the humoral response to the Sm-D fragment is, at least partially, controlled by the MHC haplotype of the recipient mice, is related to dose and type of immunogen, and is also influenced by the presence of Freund's adjuvant. It is evident that although the sera of many SLE patients recognize either or both the 1-20 and 44-67 peptides, these peptides when injected into MRL/lpr mice are not directly pathogenic.
Lupus 1997
PMID:Immunogenic properties of synthetic fragments of Sm-D protein in normal and lupus mice. 936 25

BXSB mice spontaneously develop a lupus-like syndrome that is accelerated by the Yaa gene (Y-linked autoimmune accelerator). We studied the phenotype of disease in (B10 x BXSB)F1 and (BXSB x (B10 x BXSB)F1) backcross mice and genotyped 224 backcross animals to allow a microsatellite-based genome-wide linkage analysis to be conducted. In the backcross population, three intervals on chromosome 1 showed significant linkage to disease, suggesting that multiple loci contribute to the production of autoimmune disease. D1Mit5 at 32.8 cM was linked to development of nephritis (chi(2) = 15.68, p = 7.5 x 10(-5)), as was D1Mit12 at 63.1 cM (chi(2) = 20.17, p = 7.1 x 10(-6)). D1Mit403 at 100 cM was linked to anti-dsDNA Ab production (chi(2) = 17.28, p = 3.2 x 10(-5)). Suggestive linkages to antinuclear Abs and nephritis were identified on chromosome 3, to splenomegaly on chromosome 4, and to anti-ssDNA Ab production on chromosome 10. Chromosome 4 and the telomeric region of chromosome 1 have previously been linked to disease in other mouse models of systemic lupus erythematosus; however, the centromeric regions of chromosome 1 and chromosomes 3 and 10 are unique to BXSB. This implies that, though some loci may be common to a number of mouse models of lupus, different clusters of disease genes confer disease susceptibility in different strains of mice.
 ...
PMID:Multiple lupus susceptibility loci map to chromosome 1 in BXSB mice. 974 33

Hybrids of New Zealand Black (NZB) and New Zealand White (NZW) mice spontaneously develop a disease similar to human systemic lupus erythematosus. MHC and non-MHC genes contribute to disease susceptibility in this murine model. Multiple studies have shown that the NZW H2z locus is strongly associated with the development of lupus-like disease in these mice. The susceptibility gene(s) within H2z is not known, but different lines of evidence have pointed to class II MHC genes, either H2-E or H2-A (Ez or Az in NZW). Recent studies from our laboratory showed that Ez does not supplant H2z in the contribution to lupus-like disease. In the present work we generated C57BL/10 (B10) mice transgenic for Aaz and Abz genes (designated B10.Az mice) and used a (B10.Az x NZB)F1 x NZB backcross to assess the contributions of Az genes to disease. A subset of backcross mice produced high levels of IgG autoantibodies and developed severe nephritis. However, no autoimmune phenotype was linked to the Az transgenes. Surprisingly, in the same backcross mice, inheritance of H2b from the nonautoimmune B10 strain was strongly linked with both autoantibody production and nephritis. Taken together with our previous Ez studies, the present work calls into question the importance of class II MHC genes for lupus susceptibility in this model and provides new insight into the role of MHC in lupus-like autoimmunity.
 ...
PMID:Analysis of MHC class II genes in the susceptibility to lupus in New Zealand mice. 1007 4


1 2 3 4 Next >>