Defensins in neonatal mouse intestine: epithelial gene expression
precedes the appearance of morphologically distinct paneth cells.
Darmoul, Dalila, Dennis Brown, Michael E. Selsted, and Andre J.
Ouellette.
Gastrointestinal and Renal Units, Medical Services, Massachusetts
General Hospital, and Department of Medicine, Harvard Medical School,
Boston, Massachusetts 02114, and Departments of Pathology and
Microbiology & Molecular Genetics, University of California
College of Medicine, Irvine, California 92717
APStracts 3:0165G, 1996.
In rodents, the four intestinal epithelial cell lineages differentiate
and become morphologically distinct during the first 2-3 postnatal
weeks. In studies reported here, RT-PCR-based assays detected Paneth
cell defensin mRNAs in intestinal RNA from one day-old (P1) mice,
prior to crypt formation and maturation of the epithelium. Analysis
of these defensin-coding RT-PCR products from P1 mice showed that 69%
of clones sequenced coded for cryptdin-6, suggesting that it is the
most abundant enteric defensin mRNA in the newborn. Paneth cell mRNAs
including cryptdins 4 and 5, lysozyme, matrilysin, and defensin
-related sequences also were de tected in RNA from P1 mouse intestine.
Unlike adult mice where only Paneth cells are immunopositive for
cryptdin, cryptdin-containing cells were distributed throughout the
newborn intestinal epithelium and not in association with rudimentary
crypts. Cryptdin immunoreactivity in the P1 mouse intestine was
specific for intracellular granule con tents, and immunofluorescent
detection of cryptdins on mucosal surfaces suggested that the
peptides are released into the intestinal lumen in P1 mice. Defensin
secretion may contribute to innate immunity of the neonatal intestine
prior to the presence of distin guishable Paneth cells.
Received 17 June 1996; accepted in final form 17 August 1996.
APS Manuscript Number G242-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996