A genetic locus complements resistance to Bordetella pertussis-induced histamine sensitization.

Autor: Raza A; Department of Medicine, University of Vermont, Burlington, VT, 05405, USA., Diehl SA; Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT, 05405, USA., Krementsov DN; Department of Biomedical and Health Sciences, University of Vermont, Burlington, VT, 05405, USA., Case LK; The Jackson Laboratory, Bar Harbor, ME, 04609, USA., Li D; Department of Biomedical Science, Florida Atlantic University, Boca Raton, FL, 33431, USA., Kost J; Catalytic Data Science, Charleston, SC, 29403, USA., Ball RL; The Jackson Laboratory, Bar Harbor, ME, 04609, USA., Chesler EJ; The Jackson Laboratory, Bar Harbor, ME, 04609, USA., Philip VM; The Jackson Laboratory, Bar Harbor, ME, 04609, USA., Huang R; School of Life Sciences, University of the Chinese Academy of Sciences, 100049, Beijing, China., Chen Y; School of Life Sciences, University of the Chinese Academy of Sciences, 100049, Beijing, China., Ma R; School of Life Sciences, University of the Chinese Academy of Sciences, 100049, Beijing, China., Tyler AL; Department of Biomedical and Health Sciences, University of Vermont, Burlington, VT, 05405, USA., Mahoney JM; The Jackson Laboratory, Bar Harbor, ME, 04609, USA.; Department of Neurological Sciences, Larner College of Medicine, University of Vermont, Burlington, VT, USA., Blankenhorn EP; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, 19129, USA., Teuscher C; Department of Medicine, University of Vermont, Burlington, VT, 05405, USA. c.teuscher@med.uvm.edu.; Pathology and Laboratory Medicine, University of Vermont, Burlington, VT, 05405, USA. c.teuscher@med.uvm.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2023 Mar 06; Vol. 6 (1), pp. 244. Date of Electronic Publication: 2023 Mar 06.
DOI: 10.1038/s42003-023-04603-w
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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