title: Restricted localization of claudin-16 at the tight junction in the thick ascending limb of Henle's loop together with claudins 3, 4, and 10 in bovine nephrons.
abstract: Claudin-16 is one of the tight junction protein claudins and has been shown to contribute to reabsorption of divalent cations in the human kidney. In cattle, total deficiency of claudin-16 causes severe renal tubular dysplasia without aberrant metabolic changes of divalent cations, suggesting that bovine claudin-16 has some roles in renal tubule formation and paracellular transport that are somewhat different from those expected from the pathology of human disease. As the first step to clarify these roles, we examined the expression and distribution of claudin-16 and several other major claudin subtypes, claudins 1-4 and 10, in bovine renal tubular segments by immunofluorescence microscopy. Claudin-16 was exclusively distributed to the tight junction in the tubular segment positive for Tamm-Horsfall glycoprotein, the thick ascending limb (TAL) of Henle's loop, and was found colocalized with claudins 3, 4, and 10. This study also demonstrates that bovine kidneys possess segment-specific expression patterns for claudins 2-4 and 10 that are different from those reported for mice. Particularly, distribution of claudin-4 in the TAL and distal convoluted tubules was characteristic of bovine nephrons as were differences in the expression patterns of claudins 2 and 3. These findings demonstrate that the total lack of claudin-16 in the TAL segment is the sole cause of renal tubular dysplasia in cattle and suggest that the tight junctions in distinct tubular segments including the TAL have barrier functions in paracellular permeability that are different among animal species.
authors.affiliation: Laboratory of Molecular Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohta
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Adachi
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Inaba
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle / Q000378:metabolism*; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D015870:Gene Expression; D008138:Loop of Henle / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence / Q000662:veterinary; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000662:veterinary; D013045:Species Specificity; D019108:Tight Junctions / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C568108:CLDN1 protein, human; C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; C568113:Cldn1 protein, mouse; C568123:Cldn3 protein, mouse; C568158:Cldn4 protein, mouse; D008565:Membrane Proteins; C502009:claudin 10; C502010:claudin 16