PMID- 21041494 OWN - NLM STAT- MEDLINE DCOM- 20110125 LR - 20240320 IS - 1098-5522 (Electronic) IS - 0019-9567 (Print) IS - 0019-9567 (Linking) VI - 79 IP - 1 DP - 2011 Jan TI - Strain-specific polymorphisms in Paneth cell alpha-defensins of C57BL/6 mice and evidence of vestigial myeloid alpha-defensin pseudogenes. PG - 459-73 LID - 10.1128/IAI.00996-10 [doi] AB - Paneth cells at the base of small intestinal crypts secrete microbicidal alpha-defensins, termed cryptdins (Crps) in mice, as mediators of innate immunity. Proteomic studies show that five abundant Paneth cell alpha-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 alpha-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, alpha-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 alpha-defensin pseudogenes that are closely related to functional myeloid alpha-defensin genes in the rat, suggesting that the neutrophil alpha-defensin defect in mice resulted from progressive gene loss. Given the role of alpha-defensins in shaping the composition of the enteric microflora, such polymorphisms may influence outcomes in mouse models of disease or infection. FAU - Shanahan, Michael T AU - Shanahan MT AD - 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. FAU - Tanabe, Hiroki AU - Tanabe H FAU - Ouellette, Andre J AU - Ouellette AJ LA - eng GR - R01 AI059346/AI/NIAID NIH HHS/United States GR - R01 DK044632/DK/NIDDK NIH HHS/United States GR - AI059346/AI/NIAID NIH HHS/United States GR - DK044632/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20101101 PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (alpha-Defensins) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Gene Expression Regulation/physiology MH - Intestine, Small/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Molecular Sequence Data MH - Myeloid Cells/metabolism MH - Paneth Cells/*metabolism MH - Phylogeny MH - Polymorphism, Genetic MH - Pseudogenes MH - Rats MH - alpha-Defensins/*genetics/*metabolism PMC - PMC3019906 EDAT- 2010/11/03 06:00 MHDA- 2011/01/28 06:00 PMCR- 2011/07/01 CRDT- 2010/11/03 06:00 PHST- 2010/11/03 06:00 [entrez] PHST- 2010/11/03 06:00 [pubmed] PHST- 2011/01/28 06:00 [medline] PHST- 2011/07/01 00:00 [pmc-release] AID - IAI.00996-10 [pii] AID - 0996-10 [pii] AID - 10.1128/IAI.00996-10 [doi] PST - ppublish SO - Infect Immun. 2011 Jan;79(1):459-73. doi: 10.1128/IAI.00996-10. Epub 2010 Nov 1.