| First Author | Tamura A | Year | 2008 |
| Journal | Gastroenterology | Volume | 134 |
| Issue | 2 | Pages | 523-34 |
| PubMed ID | 18242218 | Mgi Jnum | J:135596 |
| Mgi Id | MGI:3794157 | Doi | 10.1053/j.gastro.2007.11.040 |
| Citation | Tamura A, et al. (2008) Megaintestine in claudin-15-deficient mice. Gastroenterology 134(2):523-34 |
| abstractText | 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. |
