A molecular genetic linkage map of mouse chromosome 19, including thelpr, Ly-44, andTdt genes

Abstract

The mouse lpr gene, which is an autosomal recessive gene causing autoimmune disease with features of human systemic lupus erythematosus and eventually death from severe immune-complex glomerulonephritis, has been mapped on chromosome 19. To determine its exact chromosomal location, a three-point backcross was carried out by mating (MRL/MpJ-lpr/lpr x MOL-MIT)F1 x MRL/MpJ-lpr/lpr using the genes Ly-44 (lymphocyte differentiation antigen-44) and Tdt (terminal deoxynucleotidyl transferase) as markers. The following order of genes is proposed, with the distances between genes given in parentheses: centromere-Ly-44 (19.3 cM)-lpr (6.1 cM)-Tdt-telomere. The Ly-44a and Tdta alleles are found in all laboratory strains and in the wild Western European subspecies, domesticus and brevirostris. In contrast, the Ly-44b and Tdtb alleles are found in some Asian subspecies, Chinese mice of wild origin, yamashinai and molossinus. Furthermore the third Tdt allele, Tdtc, is detected in castaneus.

Sex affects immunity

“…The inability to remove or process dying cells has been suggested as a pathological mechanism driving SLE and likely accounts for the increased production of anti-nuclear antibodies. Certainly, mice defective in apoptosis develop SLE-like symptoms [99,100]. SLE patients have defects in both phagocytosis and apoptosis [101].…”

Early work on the function of CD95, an interview with Shige Nagata

“…After 2 months, Nancy reported to us that the CD95 gene was on mouse chromosome 19 at a locus near which a gene for an autosomal recessive mutation called lpr (lymphoproliferation) had recently been mapped. 20 Mice carrying homozygous mutations in lpr develop splenomegaly and lymphadenopathy. 21 The genetically mapped position of the CD95 gene was 5 cM (about 5000 kb) away from the lpr locus, but we could not abandon our naïve idea that if CD95, a receptor mediating apoptotic cell death, was mutated, cells that should die could not die, and might proliferate, causing lymphadenopathy.…”

Anti-Sm autoantibodies in systemic lupus erythematosus mice: a model system for disease-specific autoreactivity

“…Their immunopathology includes immune complex-type glomerulonephritis with a diffuse proliferative histology, vasculitis, and arthritis [1]. The lpr gene is a mutant autosomal recessive gene on chromosome 19 [74]. It has recently been shown to be the same as the Fas gene, which codes for a cell-surface receptor that can mediate apoptosis [75].…”