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Recovery from Friend disease in mice with reduced major histocompatibility complex class I expression
K J Hasenkrug1, G J Sprangrude, J Nishio
1Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840.
Abstract:
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.
Insights
Mice heterozygous for the H-2Db allele show low recovery from Friend virus infection. Reduced H-2Db expression in mice did not impact recovery, suggesting heterozygous levels are sufficient for high recovery.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Mice homozygous for the H-2Db allele show high recovery from Friend virus infections.
- Mice heterozygous for H-2Db exhibit low recovery rates, possibly due to gene dosage effects.
- Previous research suggested a need for two H-2Db alleles for effective recovery.
Purpose of the Study:
- To investigate the impact of reduced H-2Db expression on Friend disease recovery.
- To determine if heterozygous levels of H-2Db expression are sufficient for high recovery.
Main Methods:
- Utilized H-2b homozygous mice with a beta 2-microglobulin gene disruption to reduce H-2Db expression.
- Compared cell surface H-2Db expression levels in mutant mice to H-2Da/b heterozygotes.
- Assessed Friend disease recovery rates in mice with varying H-2Db expression.
Main Results:
- Beta 2-microglobulin gene disruption resulted in H-2Db expression levels comparable to H-2Da/b heterozygotes across multiple cell types.
- Reduced H-2Db expression did not negatively affect recovery from Friend disease.
- Heterozygous levels of H-2Db expression were found to be sufficient for high recovery.
Conclusions:
- The gene dosage hypothesis for H-2Db in Friend virus recovery is challenged.
- Heterozygous expression of H-2Db is sufficient for the high-recovery phenotype.
- This finding has implications for understanding MHC-mediated immune responses to viral infections.