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Gastroenterology. 2008 Feb;134(2):523-34. doi: 10.1053/j.gastro.2007.11.040. Epub 2007 Nov 28.

Megaintestine in claudin-15-deficient mice.

Author information

1
Laboratory of Biological Science, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Osaka, Japan. atsukita@biosci.med.osaka-u.ac.jp

Abstract

BACKGROUND & AIMS:

Claudins, the major components of tight junction (TJ) strands, which form paracellular barriers, consist of 24 family members, the combination of which determines the properties of TJ-based paracellular barriers. Here, we generated claudin-15-deficient (Cldn15(-/-)) mice to examine the ubiquitously expressed functions of claudin-15.

METHODS:

We generated Cldn15(-/-) mice by the conventional gene-targeting strategy. Because the upper small intestine was enlarged in Cldn15(-/-) mice, we analyzed the phenotype from various angles regarding histology, physiology, and cell biology.

RESULTS:

Cldn15(-/-) mice were born and grew normally with an enlarged upper small intestinal phenotype, megaintestine. Deficiency of claudin-15 did not cause a compensatory increase in the background expression of other types of claudins, claudin-1, -2, -3, -4, -7, -12, -18, -20, and -23, in the small intestine. Cldn15(-/-) mice showed enhanced proliferation of normal cryptic cells after weaning without diseased states such as polyps or cancer, resulting in megaintestine, in which the upper small intestine was approximately 2 times larger than normal in length and diameter. The number of transit-amplifying cells in crypts increased approximately 2-fold. Freeze-fracture electron microscopy revealed that deficiency of claudin-15 decreased the number of TJ strands, although the electric conductance was decreased in distal segments in Cldn15(-/-) jejunum, as compared with Cldn15(+/+) littermates.

CONCLUSIONS:

Based on the specific roles of claudins in paracellular barrier formation without any direct role in cell proliferation, as previously shown in cultured epithelial cells, we propose that claudin-15-based formation of TJs to organize the microenvironment including ion conductance is important for normal-sized morphogenesis of the small intestine.

PMID:
18242218
DOI:
10.1053/j.gastro.2007.11.040
[Indexed for MEDLINE]

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