Recovery from Friend disease in mice with reduced major histocompatibility complex class I expression.
Mice homozygous for the b allele of the MHC gene, H-2D, have a high incidence of recovery from Friend virus infections, while mice heterozygous for the b allele at H-2D have a very low incidence of recovery. Previous experiments indicated that the low recovery rates associated with heterozygosity at H-2D might be related to a gene dosage effect requiring the expression of two H-2Db alleles for high recovery. We investigated the effects of reduced H-2Db expression on recovery from Friend disease by using H-2b homozygous mice carrying a single beta 2-microglobulin gene disruption. These mice had reductions in cell surface H-2Db expression comparable to those of H-2Da/b heterozygotes. Numerous cell types with various levels of H-2Db expression were examined, and in each case, the expression levels in the beta 2-microglobulin mutants closely reflected those observed in the H-2Da/b heterozygotes. We found, however, that reduced expression did not affect recovery from Friend disease, indicating that heterozygous levels of H-2Db expression are sufficient for the high-recovery phenotype previously associated only with H-2Db homozygotes.
Hasenkrug
K J
KJ
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840.
Sprangrude
G J
GJ
Nishio
J
J
Brooks
D M
DM
Chesebro
B
B
D000818:Animals; D002460:Cell Line; D005622:Friend murine leukemia virus / Q000472:pathogenicity*; D005805:Genes, MHC Class I / Q000235:genetics*; D006183:H-2 Antigens / Q000235:genetics* / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology; D006579:Heterozygote; D064532:Histocompatibility Antigen H-2D; D006720:Homozygote; D007113:Immunity, Innate; D007942:Leukemia, Experimental / Q000276:immunology / Q000401:mortality*; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics; D012192:Retroviridae Infections / Q000276:immunology / Q000401:mortality*; D013163:Splenomegaly / Q000401:mortality; D013950:Thymus Gland / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology / Q000401:mortality*; D001613:beta 2-Microglobulin / Q000235:genetics
D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D001613:beta 2-Microglobulin