We have found a new spontaneous autosomal recessive mutation in mice that causes a systemic absence of lymph nodes and Peyer's patches. The name "alymphoplasia", with the gene symbol "aly", is proposed for this mutant. The spleen of aly/aly mice is devoid of well-defined lymphoid follicles, and the thymus does not show a clear cortical-medullary distinction. The mutant homozygotes are deficient in both humoral and cell-mediated immune functions, and are highly susceptible to infections. They have a reduced level of IgM and severely depressed levels of IgG and IgA in their sera, and do not reject allogeneic skin grafts. However, they have mature T and B cells as determined from their cell surface antigens. The results of bone marrow transplantation experiments suggest a mesenchymal disorder as a possible cause of the lack of lymph nodes and of immunodeficiency in the aly mouse. The aly mutant mouse may be a useful animal model of primary immunodeficiency, as are the nu (nude) and scid (severe combined immunodeficiency) mice.
Transplantation of bone marrow cells from nonobese diabetic (NOD) mice, a model for type 1 diabetes mellitus, to C3H/HeN mice, which express I-Ea molecules and have aspartic acid at residue 57 of the I-Ap chain, induced insulitis followed by overt diabetes in the recipient C3H/HeN mice more than 40 weeks after bone marrow transplantation. When cyclosporin A, which perturbs T-ceil functions, was injected intraperitoneally into [NOD -* C3H/HeN] chimeric mice daily for 1 month, the chimeric mice developed insulitis and overt diabetes within 20 weeks following bone marrow transplantation. Transplantation of bone marrow cells from (NZW x BXSB)F1 mice, which develop lupus nephritis, myocardial infarction, and idiopathic thrombocytopenic purpura, into C3H/HeN or C57BL/6J mice induced in the recipient strains both lupus nephritis and idiopathic thrombocytopenic purpura more than 3 months after transplantation.
Long-term effects of allogeneic bone marrow transplantation (ABMT) across major histocompatibility complex barriers were studied in (NZB X NZW)F1 (B/W), BXSB (6). From experiments with >100 mice using renal biopsies, autopsy analyses, and immunologic studies before and after allogeneic bone marrow transplantation (ABMT), we show herein that ABMT ameliorates established lupus nephritis in B/W mice and BXSB mice. In addition, long-term observation (from >5 mo to 1 yr post-ABMT) revealed that autoimmune diseases of BXSB and B/W mice often remained corrected for at least 1 yr after ABMT. By contrast, in MRL/lpr mice treated by ABMT from BALB/c donors, relapse of autoimmune disease regularly occurred -5 mo after ABMT.
MATERIALS AND METHODSMice. MRL/lpr, NZB, BXSB, and NZW mice obtained from The Jackson Laboratory were maintained under specific pathogen-free conditions in the animal facility
There has recently been an increase in data indicating that autoimmune mechanisms are involved in the etiopathogenesis of idiopathic thrombocytopenic purpura (ITP) (1, 2). Although antibodies that react with platelets are found in most patients with ITP, the pathogenetic nature of the antibodies remains to be clarified . The discovery of an animal model for ITP has therefore been long-awaited. Here we have found that (NZW x BXSB)Fi (W/B Fi) mice, which develop lupus nephritis with myocardial infarction (3), show thrombocytopenia with age, and that this is due to the presence ofboth platelet-associated antibodies (PAA) and circulating antiplatelet antibodies.Recently, we have demonstrated that allogeneic bone marrow transplantation (ABMT) has curative effects on autoimmune diseases in (NZB x NZW)FI, BXSB, MRL/MP-lpr/lpr (MRL/lpr), and NOD mice (4-6) . These results prompted us to examine whether ABMT can be used to treat ITP. In the present study, we provide evidence that the transplantation of bone marrow from BALB/c mice to W/B F, mice does indeed have preventative and curative effects on ITP
Materials and MethodsMice.Mice ofthe inbred strain BALB/c nu/nu, BALB/c, C57B/6, C3H/HeN, BXSB, NZW were raised under specific pathogen-free conditions in our animal facility. W/B F, males were obtained from the Nippon Shinyaku Research Laboratories, Kyoto, Japan.Staining Procedure andData Analysis.Platelet-rich plasma was obtained as described previously (7) . The platelets were suspended in 1% paraformaldehyde solution for 5 min. After
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