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The response of recombinant inbred strains of mice to bacterial lipopolysaccharides
Abstract:
Fourteen recombinant inbred strains of mice have been produced by the inbreeding of the F2 generation of a cross between C57BL/6J and C3H/HeJ progenitor mice. The responses of these BXH strains to bacterial lipopolysaccharides (LPS) have been characterized. Four BXH strains are high LPS responders and nine strains are low LPS responders. One BXH strain shows intermediate responsiveness which may reflect residual heterozygosity. F1 hybrid mice from low x high responder strains were intermediate in their response to LPS suggesting additive genetic control. The LPS responses in backcross mice from the F1 x low LPS responders showed segregation consistent with LPS responsiveness being determined by a single gene. In 13/14 BXH strains, there was concordant inheritance of LPS responsiveness and the major urinary protein locus Mup-1b. The association of the expression of the Mup-1 alleles with LPS responsiveness in the BXH strains suggests that the defective LPS response gene in C3H/HeJ mice is located on chromosome 4.
Insights
Genetic control of bacterial lipopolysaccharide (LPS) responsiveness in mice was investigated. A single gene on chromosome 4, linked to the major urinary protein locus Mup-1b, appears to determine LPS response levels in BXH strains.
Area of Science:
- Immunology
- Genetics
- Animal Models
Background:
- Bacterial lipopolysaccharides (LPS) are critical immune stimulants.
- Genetic variation influences immune responses to LPS.
- Recombinant inbred mouse strains are valuable for genetic studies.
Purpose of the Study:
- To characterize LPS responsiveness in novel BXH recombinant inbred mouse strains.
- To investigate the genetic basis of LPS responsiveness.
- To map the gene(s) controlling LPS response.
Main Methods:
- Generation of 14 BXH recombinant inbred mouse strains from C57BL/6J and C3H/HeJ progenitors.
- Phenotypic characterization of LPS responsiveness in BXH strains and F1/backcross hybrids.
- Analysis of genetic linkage with the major urinary protein locus Mup-1b.
Main Results:
- Nine BXH strains were low LPS responders, four were high responders, and one showed intermediate response.
- Additive genetic control and single-gene determination of LPS responsiveness were suggested by hybrid and backcross data.
- Concordant inheritance of LPS responsiveness and Mup-1b was observed in 13/14 strains.
Conclusions:
- LPS responsiveness in BXH mice is largely controlled by a single gene.
- This gene is likely located on chromosome 4, closely linked to the Mup-1b locus.
- The defective LPS response in C3H/HeJ mice is attributed to a gene on chromosome 4.