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CHRFAM7A expression in mice increases resiliency after injury
Todd W Costantini1, Raul Coimbra2, Jessica L Weaver3
1Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, Department of Surgery, UC San Diego School of Medicine, San Diego, CA, USA. tcostantini@health.ucsd.edu.
Summary
The CHRFAM7A gene variant improves survival and reduces lung injury in mice, suggesting it may influence the human inflammatory response to injury.
Area of Science:
- Immunology
- Genetics
- Physiology
Background:
- The CHRNA7 gene encodes the alpha-7 nicotinic acetylcholine receptor (α7nAchR), crucial for anti-inflammatory responses.
- Humans uniquely express CHRFAM7A, a variant gene that modifies α7nAchR function, with variable expression ratios in bone marrow and monocytes/macrophages.
- Previous studies showed CHRFAM7A enhances emergency myelopoiesis and lung monocyte/macrophage expression in transgenic mice.
Purpose of the Study:
- To investigate the functional impact of CHRFAM7A expression on inflammatory responses and injury resilience.
- To compare the physiological effects of CHRFAM7A in a sepsis model and a severe burn injury model.
Main Methods:
- Utilized CHRFAM7A transgenic mice and age/gender-matched wild-type (WT) siblings.
- Employed a lipopolysaccharide (LPS) injection model to assess survival rates.
- Measured lung vascular permeability following severe burn injury.
- Evaluated bone marrow CHRFAM7A expression via adoptive transfer into WT mice.
Main Results:
- CHRFAM7A expression conferred an anti-inflammatory phenotype in mice.
- Transgenic mice exhibited improved survival rates following LPS-induced sepsis.
- A significant decrease in acute lung injury was observed in CHRFAM7A transgenic mice after severe burn injury compared to WT controls.
Conclusions:
- CHRFAM7A expression is associated with enhanced resilience to injury.
- The variable expression of CHRFAM7A may contribute to individual differences in systemic inflammatory response syndrome (SIRS) to injury in humans.
