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Kidney Week

Abstract: FR-PO622

Sox2/CD63-GFP Transgenic Rat: A Novel Model for Nephrogenic Diabetes Insipidus

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Yoshimura, Aya, Fujita Health University, Toyoake, Japan
  • Shirozu, Takahiro, Fujita Health University, Toyoake, Japan
  • Kugita, Masanori, Fujita Health University, Toyoake, Japan
  • Kumamoto, Kanako, Fujita Health University, Toyoake, Japan
  • Yamaguchi, Tamio, Suzuka University of Medical Science, Suzuka, Japan
  • Nagao, Shizuko, Fujita Health University, Toyoake, Japan
Background

Tetraspanins are transmembrane proteins with four membrane domains that form complexes with other membrane proteins, playing diverse roles in physiological functions. The tetraspanins CD9, CD63, and CD81 are well-established exosome markers, while CD151 variants have been associated with glomerular disease. Previous studies using transgenic (Tg) rats expressing CD63-GFP under the Sox2 promoter, aimed at visualizing exosomes, revealed prominent symptoms of polydipsia and polyuria (Yoshimura et al., Disease Models & Mechanisms, 2018). This study aims to explore the pathophysiological characteristics of Tg (Sox2/CD63-GFP) rats.

Methods

We assessed body weight, food consumption, water intake, blood pressure, serum urea nitrogen (UN), creatinine (Cre), urine volume, and urine osmolality in Sox2/CD63-GFP rats, along with age- and sex-matched normal littermates. Histological and immunohistochemical analyses of the kidneys were conducted.

Results

Tg rats exhibited lower body weight compared to normal rats, along with approximately 7-8 times higher water intake and urine volume. Serum biochemical analysis indicated elevated UN and Cre levels in Tg rats, suggesting deteriorating renal function. Tg rat kidneys showed significant enlargement and symptoms of hydronephrosis. In normal rat kidneys, AQP3 was distributed laterally, while AQP2 was distributed apically in the collecting ducts. In contrast, Sox2/CD63-GFP rats exhibited reduced AQP2 expression in both the plasma membrane and cytoplasm of the cortical collecting ducts.

Conclusion

Nephrogenic diabetes insipidus, one of the two primary types of diabetes insipidus, primarily results from mutations in the vasopressin receptor or AQP2 in the collecting ducts. The observed symptoms in Sox2/CD63-GFP rats resembled those of diabetes insipidus, characterized by impaired water reabsorption in the kidneys and severe renal manifestations such as polydipsia, polyuria, and hydronephrosis due to excessive urinary output. CD63-GFP expression may disrupt intracellular trafficking of AQP2, given CD63's involvement in intracellular trafficking and protein localization at the plasma membrane.

Funding

  • Government Support – Non-U.S.