| First Author | Murphy ED | Year | 1978 |
| Journal | Mouse News Lett | Volume | 58 |
| Pages | 51 | Mgi Jnum | J:13757 |
| Mgi Id | MGI:61936 | Citation | Murphy ED, et al. (1978) A new congenic inbred strain, MRL/Mp. Mouse News Lett 58:51 |
| abstractText | Full text of MNL contribution: New Inbred Strains: 1. A new congenic inbred strain: MRL/Mp-lpr/lpr, lpr/+, +/+. A spontaneous autosomal recessive mutation, lpr, (lymphoproliferation) produces massive generalized lymph node enlargement in all mice of strain MRL-lpr/lpr beginning by 8 weeks of age and progressing to over 100 times control lymph node weight by 16 weeks of age. Females die at an average age of 17 weeks and males at 22 weeks with advanced immune complex glomerulonephritis. Histologically there is a blurring of node architecture with predominant proliferation of lymphocytes with some admixed plasma cells and histiocytes. Five attempts at transplanting enlarged lymph nodes have failed, diffuse parenchymal infiltrates have not been observed, and there is no leukemic blood picture. Thus, no clear evidence of malignancy has been obtained. At 16 weeks of age 90% of lymph node cells bear the Thy-1.2 membrane alloantigen compared to 63% in +/+ controls, an increase in proportion and absolute numbers of thymic-derived lymphocytes. At this age the thymus is marginally enlarged and has an atrophic cortex. Juvenile thymectomy suppresses the development of the abnormal phenotype. Hypergammaglobulinemia and marked increases in both IgGl and IgG2a is characteristic. Both antinuclear (including anti-double stranded DNA) antibody and thymocytotoxic autoantibody are present. MRL-+/+ mice do not develop the generalized lymphoproliferative syndrome. Females die at an average age of 73 weeks of age and males at 92 weeks with chronic glomerulonephritis. Necrotizing arteritis is common and about one-sixth of the mice autopsied have reticulum cell neoplasms. Antinuclear antibodies appear in the majority of 10 month-old MRL-+/+ mice. Strain MRL developed as a by-product of a series of crosses involving strains C57BL/J, C3H/Di, AKR/J, and LG/J followed by rigid inbreeding. The strain contains an estimated 0.3%, 12.1%, 12.6%, and 75.0% of the above genomes respectively. MRL mice have the large body size of LG/J, are non-agouti (a/a) albinos (c/c), and have been typed for the following polymorphic loci: Amy-la, Car-2a, Dip-1b, Es-lb, Es-2b, Es-3c, Es-10a, Got-1a, Got-2b, Gpi-1a, Gpd-1b, Gr-1a, Hbbd, Id-1a, Ldr-1a, Mod-1a, Mod-2b, Np-1a, Pgm-1a, and Pgm-2a. The phenotype of MRL cell surface alloantigens so far determined include: H-2k, Ly-1.2, Ly-2.1, Ly-3.1, Thy-1.2, and TL. The first observation of the massive lymphoproliferation occurred in the 12th generation of inbreeding. Beginning with F13 it was possible to select both lymphoproliferative positive (MRL/l) and negative (MRL/n) sublines which have an estimated 89% of their genomes in common. Breeding tests involving F1, F2, and reciprocal backcrosses between MRL/l and MRL/n confirm the hypothesis of a single autosomal recessive gene which has been designated lpr (lymphoproliferation). None of 39 (MRL/l X MRL/n)F1 hybrids and 0/29 Fl X MRL/n backcross mice were positive. Whereas 22/41 (53.7%) of Fl X MRL/l(1) backcross and 15/57 (26.3%) of F2 mice had massive lymph node enlargement that developed by 4 months of age. The mutant gene, lpr, has been transferred to strain MRL/n (henceforth designated MRL-+/+) by 5 cycles of cross-intercross matings thus reducing the estimate of residual heterozygosity from 11% to 1%. Strain MRL-+/+ has been inbred for 32 consecutive generations as of December, 1977. MRL-+/+ breeders, paired at weaning, can be expected to produce 4.5 litters by 8 months of age with an average of 6.2 pups per litter and greater than 95% survival to weaning. (Murphy, E.D. and J. R. Roths) |
