A mutation in
C3H
CC027
Collaborative Cross
Food allergy
QTL
T-cells
Themis
eanut allergy
genetics
genotype-phenotype correlation
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
13 Sep 2023
13 Sep 2023
Historique:
pubmed:
25
9
2023
medline:
25
9
2023
entrez:
25
9
2023
Statut:
epublish
Résumé
The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, unlike C3H/HeJ (C3H) mice. To determine the genetic basis of orally-induced anaphylaxis to peanut in CC027 mice. A genetic mapping population between CC027 and C3H mice was designed to identify the genetic factors that drive oral anaphylaxis. A total of 356 CC027xC3H backcrossed mice were generated, sensitized to peanut, then challenged to peanut by oral gavage. Anaphylaxis and peanut-specific IgE were quantified for all mice. T-cell phenotyping was conducted on CC027 and five additional CC strains. Anaphylaxis to peanut was absent in 77% of backcrossed mice, with 19% showing moderate anaphylaxis, and 4% having severe anaphylaxis. A total of eight genetic loci were associated with variation in response to peanut challenge, six associated with anaphylaxis (temperature decrease) and two associated with peanut-specific IgE levels. There were two major loci that impacted multiple aspects of the severity of acute anaphylaxis, at which the CC027 allele was associated with worse outcome. At one of these loci, CC027 has a private genetic variant in the Our results demonstrate a key role for
Sections du résumé
Background
UNASSIGNED
The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, unlike C3H/HeJ (C3H) mice.
Objective
UNASSIGNED
To determine the genetic basis of orally-induced anaphylaxis to peanut in CC027 mice.
Methods
UNASSIGNED
A genetic mapping population between CC027 and C3H mice was designed to identify the genetic factors that drive oral anaphylaxis. A total of 356 CC027xC3H backcrossed mice were generated, sensitized to peanut, then challenged to peanut by oral gavage. Anaphylaxis and peanut-specific IgE were quantified for all mice. T-cell phenotyping was conducted on CC027 and five additional CC strains.
Results
UNASSIGNED
Anaphylaxis to peanut was absent in 77% of backcrossed mice, with 19% showing moderate anaphylaxis, and 4% having severe anaphylaxis. A total of eight genetic loci were associated with variation in response to peanut challenge, six associated with anaphylaxis (temperature decrease) and two associated with peanut-specific IgE levels. There were two major loci that impacted multiple aspects of the severity of acute anaphylaxis, at which the CC027 allele was associated with worse outcome. At one of these loci, CC027 has a private genetic variant in the
Conclusion
UNASSIGNED
Our results demonstrate a key role for
Identifiants
pubmed: 37745496
doi: 10.1101/2023.09.13.557467
pmc: PMC10515941
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM127000
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM135123
Pays : United States
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