The SB/Le inbred strain is homozygous for both the satin (Foxq1sa) and beige (Lystbg) mutations. Most of the immunological phenotype is due to the beige mutation. Homozygous mutant beige mice are characterized by a condition that closely resembles Chediak-Higashi disease in man and similar conditions in mink and cattle. Abnormal giant lysosomal granules occur in all tissues with granule-containing cells, including granulocytes, lymphocytes, cells of the liver, kidney, central nervous system, pancreas, and thyroid, and the ducts of most glands; in type II pneumocytes; in mast cells; and in retinal pigment epithelium. Granulocytes from beige mice show defective chemotaxis and reduced bactericidal activity. Beige mice are more susceptible than controls to pneumonitis and to various viral, bacterial, and parasitic infections. They have a severe deficiency of natural killer (NK) cells. Beige mice also have a defective cytotoxic T-cell and cytotoxic antibody response to allogeneic tumor cells. Syngeneic tumor cells grow better in beige mice than in littermate controls, an effect thought to be due to the deficiency of NK cells. Beige mice have platelet storage pool deficiency, leading to a prolonged bleeding time. The immunodeficiency of beige mutant mice has been used, especially in combination with the scid mutation (Prkdcscid), in tissue graft and disease studies. SB/Le mice are also homozygous for white-bellied agouti (Aw) and the retinal degeneration 1 mutation (Pde6brd1). The retinal degeneration 1 mutation leads to early blindness (by weaning). Quantitative RT-PCR comparing Lyst mRNA from mice with the Lystbg, Lystbg-J, or Lystbg-2J alleles has shown that mice with the Lystbg-2J allele have the greatest reduction in mRNA, and mice with the Lystbg-J allele have the least reduction (Barbosa et al. Nature 1996 382:262-265). The precise function of the Lyst protein remains undetermined. Homology searches and defective Concanabalin A induced capping have lead to the postulate that Lyst is involved in microtubule function.
