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PECAM-independent thioglycollate peritonitis is associated with a locus on murine chromosome 2
Michael A Seidman1, Tina W Chew, Alan R Schenkel
1Department of Pathology, Weill Cornell Medical College, New York, New York, United States of America.
Background:
Previous studies have demonstrated that knockout or inhibition of Platelet/Endothelial Cell Adhesion Molecule (PECAM, CD31) in a number of murine strains results in impaired inflammatory responses, but that no such phenotype is seen in the C57BL/6 (B6) murine background.
Methodology/Principal Findings:
We have undertaken a quantitative trait locus (QTL) mapping effort between FVB/n (FVB) and B6 mice deficient for PECAM to identify the gene or genes responsible for this unique feature of B6 mice. We have identified a locus on murine chromosome 2 at approximately 35.8 Mb that is strongly associated (LOD score = 9.0) with inflammatory responses in the absence of PECAM.
Conclusions/Significance:
These data potentiate further study of the diapedesis machinery, as well as potential identification of new components of this machinery. As such, this study is an important step to better understanding the processes of inflammation.
Insights
Genetic mapping identified a key locus on mouse chromosome 2 influencing inflammatory responses when Platelet/Endothelial Cell Adhesion Molecule (PECAM) is absent. This finding is crucial for understanding inflammation mechanisms in C57BL/6 mice.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Platelet/Endothelial Cell Adhesion Molecule (PECAM, CD31) knockout/inhibition impairs inflammatory responses in most mouse strains.
- C57BL/6 (B6) mice exhibit no such impairment, indicating a unique genetic basis for their inflammatory response.
Purpose of the Study:
- To identify the genetic factors responsible for the normal inflammatory response in B6 mice lacking PECAM.
- To pinpoint the specific genetic locus associated with this phenotype.
Main Methods:
- Quantitative Trait Locus (QTL) mapping was performed between FVB/n (FVB) and B6 mouse strains.
- Genetic analysis focused on mice deficient for PECAM.
Main Results:
- A significant locus associated with inflammatory responses was identified on murine chromosome 2.
- This locus is located at approximately 35.8 Mb and shows a strong association (LOD score = 9.0) in the absence of PECAM.
Conclusions:
- The identified locus is critical for understanding inflammation in PECAM-deficient B6 mice.
- These findings open avenues for further research into the diapedesis machinery and potential new components involved in inflammation.
