Strain-specific polymorphisms in Paneth cell α-defensins of C57BL/6 mice and evidence of vestigial myeloid α-defensin pseudogenes

Infect Immun. 2011 Jan;79(1):459-73. doi: 10.1128/IAI.00996-10. Epub 2010 Nov 1.

Abstract

Paneth cells at the base of small intestinal crypts secrete microbicidal α-defensins, termed cryptdins (Crps) in mice, as mediators of innate immunity. Proteomic studies show that five abundant Paneth cell α-defensins in C57BL/6 mice are strain specific in that they have not been identified in other inbred strains of mice. Two C57BL/6-specific peptides are coded for by the Defcr20 and -21 genes evident in the NIH C57BL/6 genome but absent from the Celera mixed-strain assembly, which excludes C57BL/6 data and differs from the NIH build with respect to the organization of the α-defensin gene locus. Conversely, C57BL/6 mice lack the Crp1, -2, -4, and -6 peptides and their corresponding Defcr1, -2, -4, and -6 genes, which are common to several mouse strains, including those of the Celera assembly. In C57BL/6 mice, α-defensin gene diversification appears to have occurred by tandem duplication of a multigene cassette that was not found in the mixed-strain assembly. Both mouse genome assemblies contain conserved α-defensin pseudogenes that are closely related to functional myeloid α-defensin genes in the rat, suggesting that the neutrophil α-defensin defect in mice resulted from progressive gene loss. Given the role of α-defensins in shaping the composition of the enteric microflora, such polymorphisms may influence outcomes in mouse models of disease or infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Gene Expression Regulation / physiology
  • Intestine, Small / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Myeloid Cells / metabolism
  • Paneth Cells / metabolism*
  • Phylogeny
  • Polymorphism, Genetic
  • Pseudogenes
  • Rats
  • alpha-Defensins / genetics*
  • alpha-Defensins / metabolism*

Substances

  • alpha-Defensins