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

ABSTRACT: Paneth cells at the base of small intestinal crypts secrete microbicidal ?-defensins, termed cryptdins (Crps) in mice, as mediators of innate immunity. Proteomic studies show that five abundant Paneth cell ?-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 ?-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, ?-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 ?-defensin pseudogenes that are closely related to functional myeloid ?-defensin genes in the rat, suggesting that the neutrophil ?-defensin defect in mice resulted from progressive gene loss. Given the role of ?-defensins in shaping the composition of the enteric microflora, such polymorphisms may influence outcomes in mouse models of disease or infection.

SUBMITTER: Shanahan MT 

PROVIDER: S-EPMC3019906 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature