CHRFAM7A, a human-specific and partially duplicated α7-nicotinic acetylcholine receptor gene with the potential to specify a human-specific inflammatory response to injury
- 3 December 2014
- journal article
- review article
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 97 (2), 247-257
- https://doi.org/10.1189/jlb.4ru0814-381r
Abstract
Conventional wisdom presumes that the α7nAChR product of CHRNA7 expression mediates the ability of the vagus nerve to regulate the inflammatory response to injury and infection. Yet, 15 years ago, a 2nd structurally distinct and human-specific α7nAChR gene was discovered that has largely escaped attention of the inflammation research community. The gene, originally called dupα7nAChR but now known as CHRFAM7A, has been studied exhaustively in psychiatric research because of its association with mental illness. However, dupα7nAChR/CHRFAM7A expression is relatively low in human brain but elevated in human leukocytes. Furthermore, α7nAChR research in human tissues has been confounded by cross-reacting antibodies and nonspecific oligonucleotide primers that crossreact in immunoblotting, immunohistochemistry, and RT-PCR. Yet, 3 independent reports show the human-specific CHRFAM7A changes cell responsiveness to the canonical α7nAChR/CHRNA7 ion-gated channel. Because of its potential for the injury research community, its possible significance to human leukocyte biology, and its relevance to human inflammation, we review the discovery and structure of the dupα7nAChR/CHRFAM7A gene, the distribution of its mRNA, and its biologic activities and then discuss its possible role(s) in specifying human inflammation and injury. In light of emerging concepts that point to a role for human-specific genes in complex human disease, the existence of a human-specific α7nAChR regulating inflammatory responses in injury underscores the need for caution in extrapolating findings in the α7nAChR literature to man. To this end, we discuss the translational implications of a uniquely human α7nAChR-like gene on new drug target discovery and therapeutics development for injury, infection, and inflammation.Keywords
Funding Information
- U.S. National Institutes of Health (CA170140)
- U.S. Department of Defense
- American Burn Association (W81XWH-10-1-0527)
- Exploratory Wound Healing Research (NIGM78421)
This publication has 111 references indexed in Scilit:
- Genomic responses in mouse models poorly mimic human inflammatory diseasesProceedings of the National Academy of Sciences, 2013
- A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorderHuman Genetics, 2011
- The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of α7*nAChR functionBiochemical Pharmacology, 2011
- Function of Partially Duplicated Human α7 Nicotinic Receptor Subunit CHRFAM7A GeneJournal of Biological Chemistry, 2011
- A 2-base pair deletion polymorphism in the partial duplication of the α7 nicotinic acetylcholine gene (CHRFAM7A) on chromosome 15q14 is associated with schizophreniaBrain Research, 2009
- Differentiating nicotine- versus schizophrenia-associated decreases of the α7 nicotinic acetylcholine receptor transcript, CHRFAM7A, in peripheral blood lymphocytesJournal of Neural Transmission, 2008
- Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemiaProceedings of the National Academy of Sciences, 2008
- Acetylcholine beyond neurons: the non‐neuronal cholinergic system in humansBritish Journal of Pharmacology, 2008
- The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammationBritish Journal of Pharmacology, 2007
- Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammationNature, 2002