Activity, expression and genetic variation of canine β-defensin 103

A multifunctional antimicrobial peptide in the skin of domestic dogs

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The skin functions as more than a physical barrier to infection. Epithelial cells of the skin can synthesize antimicrobial peptides, including defensins, which exhibit direct antimicrobial activity. Here we characterize the expression pattern, genetic variation and activity of the major β-defensin expressed in canine skin, canine β-defensin 103 (CBD103). The gene encoding CBD103 exhibits two forms of polymorphism: a common 3-basepair deletion allele and a gene copy-number variation. Golden retrievers and Labrador retrievers were the only breeds that encoded the variant allele of CBD103, termed CBD103ΔG23. Both these breeds also exhibited a CBD103 gene copy-number polymorphism that ranged from 2 to 4 gene-copies per diploid genome. Recombinant CBD103 and CBD103ΔG23, as well as the human ortholog human β-defensin 3 (hBD3) and hBD3ΔG23, showed potent and comparable antimicrobial killing against both methicillin-susceptible and methicillin-resistant Staphylococcus pseudintermedius. Skin biopsy specimens from dogs with atopic dermatitis revealed CBD103 expression levels similar to those in healthy controls and comparable at lesional and nonlesional sites. This expression pattern in dogs differs from the previously reported reduced expression of the human ortholog in atopic dermatitis. Overall, the similarities of CBD103 and its human ortholog reported here support the notion that the domestic dog may serve as a valuable model for studying β-defensin biology in the skin.

Original languageEnglish (US)
Pages (from-to)248-259
Number of pages12
JournalJournal of Innate Immunity
Volume4
Issue number3
DOIs
StatePublished - Apr 2012

Fingerprint

Defensins
Canidae
Dogs
Skin
Peptides
Gene Dosage
Atopic Dermatitis
Alleles
DNA Copy Number Variations
Newfoundland and Labrador
Architectural Accessibility
Methicillin Resistance
Methicillin
Diploidy
Staphylococcus
Genes
Epithelial Cells
Genome
Biopsy
Infection

Keywords

  • Antimicrobial peptides
  • Atopic dermatitis
  • Canine beta-defensin
  • Epidermis
  • Skin

ASJC Scopus subject areas

  • Immunology and Allergy

Cite this

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title = "Activity, expression and genetic variation of canine β-defensin 103: A multifunctional antimicrobial peptide in the skin of domestic dogs",
abstract = "The skin functions as more than a physical barrier to infection. Epithelial cells of the skin can synthesize antimicrobial peptides, including defensins, which exhibit direct antimicrobial activity. Here we characterize the expression pattern, genetic variation and activity of the major β-defensin expressed in canine skin, canine β-defensin 103 (CBD103). The gene encoding CBD103 exhibits two forms of polymorphism: a common 3-basepair deletion allele and a gene copy-number variation. Golden retrievers and Labrador retrievers were the only breeds that encoded the variant allele of CBD103, termed CBD103ΔG23. Both these breeds also exhibited a CBD103 gene copy-number polymorphism that ranged from 2 to 4 gene-copies per diploid genome. Recombinant CBD103 and CBD103ΔG23, as well as the human ortholog human β-defensin 3 (hBD3) and hBD3ΔG23, showed potent and comparable antimicrobial killing against both methicillin-susceptible and methicillin-resistant Staphylococcus pseudintermedius. Skin biopsy specimens from dogs with atopic dermatitis revealed CBD103 expression levels similar to those in healthy controls and comparable at lesional and nonlesional sites. This expression pattern in dogs differs from the previously reported reduced expression of the human ortholog in atopic dermatitis. Overall, the similarities of CBD103 and its human ortholog reported here support the notion that the domestic dog may serve as a valuable model for studying β-defensin biology in the skin.",
keywords = "Antimicrobial peptides, Atopic dermatitis, Canine beta-defensin, Epidermis, Skin",
author = "Leonard, {Brian C} and Marks, {Stanley L} and Outerbridge, {Catherine A} and Affolter, {Verena K} and Anchasa Kananurak and Amy Young and Moore, {Peter F} and Bannasch, {Danika L} and Bevins, {Charles L}",
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AU - Marks, Stanley L

AU - Outerbridge, Catherine A

AU - Affolter, Verena K

AU - Kananurak, Anchasa

AU - Young, Amy

AU - Moore, Peter F

AU - Bannasch, Danika L

AU - Bevins, Charles L

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N2 - The skin functions as more than a physical barrier to infection. Epithelial cells of the skin can synthesize antimicrobial peptides, including defensins, which exhibit direct antimicrobial activity. Here we characterize the expression pattern, genetic variation and activity of the major β-defensin expressed in canine skin, canine β-defensin 103 (CBD103). The gene encoding CBD103 exhibits two forms of polymorphism: a common 3-basepair deletion allele and a gene copy-number variation. Golden retrievers and Labrador retrievers were the only breeds that encoded the variant allele of CBD103, termed CBD103ΔG23. Both these breeds also exhibited a CBD103 gene copy-number polymorphism that ranged from 2 to 4 gene-copies per diploid genome. Recombinant CBD103 and CBD103ΔG23, as well as the human ortholog human β-defensin 3 (hBD3) and hBD3ΔG23, showed potent and comparable antimicrobial killing against both methicillin-susceptible and methicillin-resistant Staphylococcus pseudintermedius. Skin biopsy specimens from dogs with atopic dermatitis revealed CBD103 expression levels similar to those in healthy controls and comparable at lesional and nonlesional sites. This expression pattern in dogs differs from the previously reported reduced expression of the human ortholog in atopic dermatitis. Overall, the similarities of CBD103 and its human ortholog reported here support the notion that the domestic dog may serve as a valuable model for studying β-defensin biology in the skin.

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