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Am J Physiol Gastrointest Liver Physiol 291: G1081-G1088, 2006. First published August 10, 2006; doi:10.1152/ajpgi.00449.2005
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MUCOSAL BIOLOGY

A naturally occurring point mutation in the rat aquaporin 5 gene, influencing its protein production by and secretion of water from salivary glands

Kwartarini Murdiastuti, Nunuk Purwanti, Mileva Ratko Karabasil, Xuefei Li, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori, and Kazuo Hosoi

Department of Molecular Oral Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan

Submitted 30 September 2005 ; accepted in final form 15 July 2006

A greater than twofold diversity in the expression level of aquaporin 5 (AQP5) has been observed in the membrane fraction of the submandibular gland (SMG) in Sprague-Dawley rats (Murdiastuti K, Miki O, Yao C, Parvin MN, Kosugi-Tanaka C, Akamatsu T, Kanamori N, and Hosoi K. Pflügers Arch 445: 405–412, 2002). In the present study, breeding between brother and sister rats was repeated within high AQP5 producers and low ones to obtain inbred offspring. High- and low-producer rats from 3rd to 18th generations were used for experiments. By Western blotting, levels of AQP5 proteins in the parotid and lacrimal glands, and lungs were all low in low producers, whereas they were all high in high producers, implying genetic variations of the gene for this water channel. Despite this implication, AQP5 mRNA levels were almost the same between the two groups by Northern blotting, suggesting the irrelevance of transcriptional regulation for this diversity. AQP5 cDNAs from the SMGs of the two groups were sequenced. The nucleotide sequence of AQP5 cDNA from low producers indicated the existence of a point mutation at nt 308 (G308A), leading to a replacement of 103Gly with 103Asp in the third transmembrane domain, but no alteration was detected in the Kozak area. The existence of such a mutation was confirmed by the assessment of genomic DNA also. This mutation may have resulted in an abnormal membrane insertion or ineffective trafficking of AQP5, since the rats having this mutation showed extremely low membrane expression of AQP5 in the SMG acinar cells and decreased water secretion from their salivary glands.

water channel; salivary gland



Address for reprint requests and other correspondence: K. Hosoi, Dept. of Molecular Oral Physiology, Institute of Health Biosciences, The Univ. of Tokushima Graduate School, Kuramoto-cho, Tokushima-shi, Tokushima 770-8504, Japan (e-mail: hosoi{at}dent.tokushima-u.ac.jp)




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Am. J. Physiol. Gastrointest. Liver Physiol.Home page
X. Li, A. Azlina, M. R. Karabasil, N. Purwanti, T. Hasegawa, C. Yao, T. Akamatsu, and K. Hosoi
Degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by cevimeline, an M3 muscarinic receptor agonist
Am J Physiol Gastrointest Liver Physiol, July 1, 2008; 295(1): G112 - G123.
[Abstract] [Full Text] [PDF]




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