アクアポリン5 シゼン ハッセイ イデンシ ヘンイ ノ ミズ チャネル キノウ ニ オヨボス エイキョウ
Effects of a Naturally Occurring Mutation in Rat Aquaporin 5 on its Water Channel Functions
The aquaporin (AQP) family in mammals is composed of 13 members (AQP0-12) of
water channel proteins. One of them, AQP5, is expressed in the various exocrine glands such as the lachrymal, parotid, and submandibular gland, and also in lung. We found the presence of G>A point mutation at position 308 in the rat AQP5 mRNA as well as the genome DNA. This mutation resulted in replacement of Gly103 with Asp103 in the AQP5 protein molecule, and led to various phenotypic alterations in the salivary gland. The point mutation localized in the 3rd trans-membrane domain, which is remote site from the water pore. As expected, the water permeability of the mutant molecule was almost same as that of the wild type molecule, indicating that the mutation does not affect the water permeability. In the submandibular gland, membrane expression of the mutant molecule was extremely reduced; and the secretion of saliva in the mutant rat was reduced also as compared to the wild-type animals. By confocal immunohistochemistry, an increased association of AQP5 and lysosomal markers, Lamp2 and/or cathepsin D was observed in the cytoplasmic area of acinar cells of mutant rats, implying the accelerated metabolism of the mutant molecule by the lysosomal system.
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