| First Author | Murphy ED | Year | 1982 |
| Journal | Mouse News Lett | Volume | 67 |
| Pages | 20-1 | Mgi Jnum | J:29572 |
| Mgi Id | MGI:77345 | Citation | Murphy ED, et al. (1982) Generalized lymphoproliferative disease (gld). Mouse News Lett 67:20-1 |
| abstractText | Full text of MNL contribution: Research News. 1. Generalized lymphoproliferative disease (gld). A new autosomal recessive mutation designated generalized lymphoproliferative disease (gld) has been discovered in strain C3H/HeJ. The foremost phenotypic aberration is that of massive enlargement of all lymph nodes. By 20 weeks of age lymph nodes are 50-fold heavier than those of coisogenic C3H/HeJ-+/+ control mice. Spleens are enlarged 4-fold. There is no significant difference in thymus weight. Mutant gld/gld mice have normal erythrocyte numbers but a 5-fold increase in peripheral blood lymphocytes. Analysis of lymphocyte subsets by immunofluorescence microscopy and cytofluorometry indicate an increase in Thy-1 positive lymphocytes (T cells) from 59 to 68 percent, a decrease in frequency of surface immunoglobulin-bearing lymphocytes (B cells) from 36 to 15 percent and an increase in mononuclear cells that have neither marker (Null cells) from 5.5 to 17 percent. Serologically, gld/gld mice develop a broad-based hypergammaglobulinemia with at least 10-fold elevations in both serum IgA and IgG2a and 3 to 6-fold elevations in IgGl, IgG2b, and IgM levels. High titers of antinuclear auto-antibodies including anti-dsDNA are evident by 14 weeks of age. Mutant gld/gld mice live only one-half as long as controls, 54 weeks\ compared to 98 weeks of age. There is no significant sex difference in lifespan nor any other endpoint so far measured. At autopsy, common findings include nephritic, hepatitic, and-pulmonary lesions. Deposits of immune complexes in the renal glomerulus have been identified. This pattern of early-onset massive lymph node enlargement and production of antinuclear autoantibody resembles the syndrome induced by another autosomal recessive mutation, lymphoproliferation, lpr (Murphy and Roths, MNL 58:51-52, 1978). Genetic investigation indicates that the mutations gld and lpr are not allelic. Linkage studies have placed gld on Chromosome 1 between Pep-3 and Lp. This new mutation adds another genetically well-defined model to the list of lymphoproliferative diseases that may be exploited to gain a clearer understanding of the nature of immunoregulatory defects and the role of such aberrations in the pathogenesis of systemic autoimmune disease. (E.D. Murphy, J.B. Roths, and Eicher) |
