Uniquely human CHRFAM7A gene increases the hematopoietic stem cell reservoir in mice and amplifies their inflammatory response
Abstract
The emergence of uniquely human genes during hominid speciation enabled numerous human-specific adaptations that presumably included changes in resilience to disease but potentially increased susceptibility as well. Here we show that the transgenic expression of one such gene, called CHRFAM7A, changes the mouse reservoir of hematopoietic stem cells in bone marrow and amplifies the mouse inflammatory response in a model of human systemic inflammatory response syndrome (SIRS). Because the CHRFAM7A gene is a dominant-negative inhibitor of ligand binding to α7 nicotinic acetylcholine receptor (α7nAChR), a neurotransmitter receptor implicated in immunity, inflammation, neurodegeneration, and cognitive function, the results underscore the importance of understanding the contribution of species-specific genes to human disease and the impact they may have on the fidelity of animal models for translational medicine.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 03, 2019
- Source ID
- 10.1073/pnas.1821853116
Entities
People
- Andrew Baird
- Brian P Eliceiri
- Elliot Williams
- Olga Cohen
- Sabrina Treadwell
- Simone Langness
- Theresa W. Chan
- Todd W. Costantini
Organizations
- National Institutes of Health
- United States Department of Defense
- University of California, San Diego