Autoimmune Disease in New Zealand Mice

Abstract

Because the pathogenic mechanisms of spontaneous autoimmune diseases in human patients have not been elucidated, researchers have studied animal models with the expectation that their experimental accessibility and defined genetic scope will facilitate understanding of the autoimmune process. These efforts have focused on several lines of inbred mice that spontaneously develop genetically conditioned autoimmune disease. Our work emphasizes the study of New Zealand mice, because their clinical disorders and genetic complexity most closely resemble human disease. Several strains of New Zealand mice were inbred, selecting for coat color, by Dr. Marianne Beilschowsky at the University of Otago in Dunedin, New Zealand during the 1950s. In the eleventh inbred generation, it was noted that the mice of the New Zealand Black (NZB) strain developed autoimmune hemolytic anemia — the first animal model of autoimmune disease [1, 2]. Subsequent crosses with other strains revealed that the F₁ hybrid of NZB with New Zealand White (NZW) mice develops lupus erythematosus in which anti-DNA and anti-gp70 autoantibodies cause immune complex glomerulonephritis [3]. Interestingly, the NZW strain is immunologically normal, at least until very late in life. As in most human autoimmune disorders, female (NZB × NZW) F₁ mice are more severely affected than males. The results of castration and sex hormone replacement experiments have shown that this is a hormonal effect [4, 5].