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Significance Genetic variations can affect the immune response to infectious conditions. Recent evidence shows DNA copy number variations (CNVs) in the DEFA1A3 locus, which encodes for human neutrophil peptides 1-3… Click to show full abstract
Significance Genetic variations can affect the immune response to infectious conditions. Recent evidence shows DNA copy number variations (CNVs) in the DEFA1A3 locus, which encodes for human neutrophil peptides 1-3 (HNP1-3) are associated with urinary tract infections (UTIs). A manipulatable human DEFA4/4 gene transgenic mouse model allows further characterization of UTI and pyelonephritis susceptibility. In this study, we demonstrate the expression of DEFA1A3 in the transgenic human DEFA4/4 mouse mirrors human urinary tract DEFA1A3 expression. We also demonstrate this transgenic mouse is protected from uropathogenic Escherichia coli (UPEC) challenges. Additionally, in vitro assays using HNP1-3 against UPEC elucidate combinational effects when used with other antimicrobial peptides. Our models allow for future studies in precision medicine and novel therapeutic development.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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