Strain-specific polymorphisms in Paneth cell α-defensins of C57BL/6 mice and evidence of vestigial myeloid α-defensin pseudogenes.
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.
Department of Pathology and Laboratory Medicine, Keck School of Medicine of the University of Southern California, USC Norris Cancer Center, NRT 7514, 1450 Biggy Street, Los Angeles, CA 90089-9601, USA.
Michael T
MT
Shanahan
Hiroki
H
Tanabe
André J
AJ
Ouellette
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation / Q000502:physiology; D007421:Intestine, Small / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000378:metabolism; D019879:Paneth Cells / Q000378:metabolism*; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011544:Pseudogenes; D051381:Rats; D023084:alpha-Defensins / Q000235:genetics* / Q000378:metabolism*
D023084:alpha-Defensins