Novel treatment for lithium-induced nephrogenic diabetes insipidus rat model using the Sendai-virus vector carrying aquaporin 2 gene

Hidetaka Suga, Hiroshi Nagasaki, Taka Aki Kondo, Yoshiki Okajima, Chizuko Suzuki, Nobuaki Ozaki, Hiroshi Arima, Tokunori Yamamoto, Noriyuki Ozaki, Masaro Akai, Aiko Sato, Nobuyuki Uozumi, Makoto Inoue, Mamoru Hasegawa, Yutaka Oiso

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Congenital nephrogenic diabetes insipidus (NDI) is a chronic disorder involving polyuria and polydipsia that results from unresponsiveness of the renal collecting ducts to the antidiuretic hormone vasopressin. Either of the genetic defects in vasopressin V2 receptor or the water channel aquaporin 2 (AQP2) cause the disease, which interfere the water reabsorption at the epithelium of the collecting duct. An unconscious state including a perioperative situation can be life threatening because of the difficulty to regulate their water balance. The Sendai virus (SeV) vector system deleting fusion protein (F) gene (SeV/ΔF) is considered most suitable because of the short replication cycle and nontransmissible character. An animal model for NDI with reduced AQP2 by lithium chloride was used to develop the therapy. When the SeV/ΔF vector carrying a human AQP2 gene (AQP2-SeV/ΔF) was administered retrogradely via ureter to renal pelvis, AQP2 was expressed in the renal collecting duct to reduce urine output and water intake by up to 40%. In combination with the retorograde administration to pelvis, this system could be the cornerstone for the applicable therapies on not only NDI patients but also other diseases associate with the medullary collecting duct.

Original languageEnglish
Pages (from-to)5803-5810
Number of pages8
JournalEndocrinology
Volume149
Issue number11
DOIs
Publication statusPublished - 2008 Nov

ASJC Scopus subject areas

  • Endocrinology

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    Suga, H., Nagasaki, H., Kondo, T. A., Okajima, Y., Suzuki, C., Ozaki, N., Arima, H., Yamamoto, T., Ozaki, N., Akai, M., Sato, A., Uozumi, N., Inoue, M., Hasegawa, M., & Oiso, Y. (2008). Novel treatment for lithium-induced nephrogenic diabetes insipidus rat model using the Sendai-virus vector carrying aquaporin 2 gene. Endocrinology, 149(11), 5803-5810. https://doi.org/10.1210/en.2007-1806