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Journal article
A genetic locus complements resistance to Bordetella pertussis-induced histamine sensitization
Communications biology, v 6(1), 244
06 Mar 2023
PMID: 36879097
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Histamine plays pivotal role in normal physiology and dysregulated production of histamine or signaling through histamine receptors (HRH) can promote pathology. Previously, we showed that
Bordetella pertussis
or pertussis toxin can induce histamine sensitization in laboratory inbred mice and is genetically controlled by
Hrh1
/HRH1. HRH1 allotypes differ at three amino acid residues with P
263
-V
313
-L
331
and L
263
-M
313
-S
331
, imparting sensitization and resistance respectively. Unexpectedly, we found several wild-derived inbred strains that carry the resistant HRH1 allotype (L
263
-M
313
-S
331
) but exhibit histamine sensitization. This suggests the existence of a locus modifying pertussis-dependent histamine sensitization. Congenic mapping identified the location of this modifier locus on mouse chromosome 6 within a functional linkage disequilibrium domain encoding multiple loci controlling sensitization to histamine. We utilized interval-specific single-nucleotide polymorphism (SNP) based association testing across laboratory and wild-derived inbred mouse strains and functional prioritization analyses to identify candidate genes for this modifier locus.
Atg7, Plxnd1, Tmcc1, Mkrn2, Il17re, Pparg, Lhfpl4, Vgll4, Rho and Syn2
are candidate genes within this modifier locus, which we named
Bphse
, enhancer of Bordetella pertussis induced histamine sensitization. Taken together, these results identify, using the evolutionarily significant diversity of wild-derived inbred mice, additional genetic mechanisms controlling histamine sensitization.
Mice with the histamine sensitization resistant alleles are still susceptible to histamine shock, with a locus on chromosome 6 associated with histamine sensitization reported.
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Details
- Title
- A genetic locus complements resistance to Bordetella pertussis-induced histamine sensitization
- Creators
- Abbas Raza - University of VermontSean A. Diehl - University of VermontDimitry N. Krementsov - University of VermontLaure K. Case - Jackson LaboratoryDawei Li - Florida Atlantic UniversityJason Kost - Catalytic Materials (United States)Robyn L. Ball - Jackson LaboratoryElissa J. Chesler - Jackson LaboratoryVivek M. Philip - Jackson LaboratoryRui Huang - University of Chinese Academy of SciencesYan Chen - University of Chinese Academy of SciencesRunlin Ma - University of Chinese Academy of SciencesAnna L. Tyler - University of VermontJ. Matthew Mahoney - Jackson LaboratoryElizabeth P. Blankenhorn - Drexel UniversityCory Teuscher - University of Vermont
- Publication Details
- Communications biology, v 6(1), 244
- Publisher
- Nature Publishing Group UK
- Number of pages
- 11
- Grant note
- ; RR-1602-07780 / ; R21 LM012615 / ; R21 AI145306; R21 AI145306 / ; R01 DA028420 / ; P20GM130454 / ; U54 OD030187 / ;
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000943962200001
- Scopus ID
- 2-s2.0-85149991408
- Other Identifier
- 991020183539704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biology