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- W3195201783 abstract "A bstract Histamine is a bioactive amine associated with a plethora of normal and pathophysiological processes, with the latter being dependent on both genetic and environmental factors including infectious agents. Previously, we showed in mice that susceptibility to Bordetella pertussis and pertussis toxin (PTX) induced histamine sensitization (Bphs) is controlled by histamine receptor H 1 ( Hrh1 /HRH1) alleles. Bphs susceptible and resistant alleles ( Bphs s / Bphs r ) encode for two-conserved protein haplotypes. Given the importance of HRH1 signaling in health and disease, we sequenced Hrh1 across an extended panel of laboratory and wild-derived inbred strains and phenotyped them for Bphs. Unexpectedly, eight strains homozygous for the Bphs r allele phenotyped as Bphs s , suggesting the existence of a modifying locus segregating among the strains capable of complementing Bphs r . Genetic analyses mapped this modifier locus to mouse chromosome 6; designated Bphs -enhancer ( Bphse ), within a functional linkage disequilibrium domain encoding multiple loci controlling responsiveness to histamine ( Bphs / Hrh1 and Histh1-4 ). Interval-specific single-nucleotide polymorphism (SNP) based association testing across 50 laboratory and wild-derived inbred mouse strains and functional prioritization analyses resulted in the identification of candidate genes for Bphse within a ∼5.5 Mb interval (Chr6:111.0-116.4 Mb), including Atg7, Plxnd1, Tmcc1, Mkrn2, Il17re, Pparg, Lhfpl4, Vgll4, Rho and Syn2 . Taken together, these results demonstrate the power of combining network-based computational methods with the evolutionarily significant diversity of wild-derived inbred mice to identify novel genetic mechanisms controlling susceptibility and resistance to histamine shock." @default.
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- W3195201783 date "2021-08-18" @default.
- W3195201783 modified "2023-09-27" @default.
- W3195201783 title "Genetic Analysis of Bphse: a Novel Gene Complementing Resistance to Bordetella pertussis-Induced Histamine Sensitization" @default.
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- W3195201783 doi "https://doi.org/10.1101/2021.08.18.456822" @default.
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