B6.C3Rl-Lyst^bg/J

Stock number: 000204
Research areas: Cardiovascular Research, Dermatology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Metabolism Research, Mouse/Human Gene Homologs, Research Tools

Detailed description

Mice homozygous for the beige spontaneous mutation (Lyst^bg) 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 homozygous mutant mice 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. Natural killer (NK) cells from beige mice exhibit decreased endogenous cytotoxic activity. 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 (Prkdc^scid), in tissue graft and disease studies.

Development

Both the satin (Foxq1^sa) and the original beige (Lyst^bg) recessive mutations arose at Oak Ridge National Laboratory in backcross test matings from T stock female x irradiated (101/Rl x C3H/Rl)F1 male. T stock was a multiple-recessive tester strain that contained several backgrounds including C57BL10/Rl. The two separate mutations, Foxq1^sa and Lyst^bg, were bred together and homozygous A^w/A^w Foxq1^sa Lyst^bg/Foxq1^sa Lyst^bg mice on a mixed background were received at The Jackson Laboratory in 1961. From the 5 mice imported one pair was bred brother x sister, both homozygous for Foxq1^sa, Lyst^bg and A^w, and this stock became strain SB/Le in 1971 at F42. The other mated pair was backcrossed to C57BL/6J keeping Foxq1^sa and Lyst^bg in coupling by the cross intercross system to N6. This stock was then sib mated to N6 F29 before 5 more backcrosses to C57BL/6J were made. At N11 Foxq1^sa was removed from the strain and sib matings of bg to N11F8 were made before 2 more crosses to C57BL/6J, made the stock N13 in 1982. The stock was cryopreserved in 1986 by mating homozygous Lyst^bg males at N13F16 to C57BL/6J females.

Allele

Symbol: Lyst^bg
Name: beige
MGI accession ID: MGI:1855968
Generation method: Radiation induced
Marker symbol: Lyst
Marker name: lysosomal trafficking regulator
Chromosome: 13
Strain of origin: C3H/Rl
Molecular note: This allele is an insertion of a partial LINE 1 repetitive element into an intron of the gene. The insertion included only the most 3' 1097 bp of the element producing a frameshift mutation resulting in a truncated protein predicted to be missing the last 1442 amino acids.