Abstract: SA-PO0280
Development of Model Animals Suitable for Analyzing the Pathogenesis of CKD-MBD
Session Information
- Bone and Mineral Metabolism: Basic Research
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 501 Bone and Mineral Metabolism: Basic
Authors
- Komiya, Aoi, Tokushima University, School of Medicine, Tokushima, Japan
- Koike, Megumi, Tokushima University, School of Medicine, Tokushima, Japan
- Higashi, Ayami, Tokushima University, School of Medicine, Tokushima, Japan
- Tanii, Ryuka, Tokushima University, School of Medicine, Tokushima, Japan
- Ohmori, Minori, Tokushima University, School of Medicine, Tokushima, Japan
- Shibahara, Shion, Tokushima University, School of Medicine, Tokushima, Japan
- Shiozaki, Yuji, Tokushima University, School of Medicine, Tokushima, Japan
- Matsusaka, Taiji, Tokai University, School of Medicine, Tokai, Japan
- Segawa, Hiroko, Tokushima University, School of Medicine, Tokushima, Japan
Background
Chronic kidney disease–mineral and bone disorder (CKD-MBD) represents a systemic complication of chronic kidney disease, contributing significantly to increased morbidity and mortality. Several experimental models of CKD-MBD have been widely used to induce CKD-MBD-like phenotypes. However, in patients with CKD, renal dysfunction is frequently driven by glomerular pathology, and existing models fail to recapitulate the complex pathophysiology of CKD-MBD. Thus, establishing a pathophysiologically relevant animal model is imperative for elucidating the mechanisms underlying CKD-MBD and developing effective therapeutic interventions. In this study, we aimed to establish a mouse model of CKD-MBD that recapitulates human pathophysiology, using Nephrin-hCD25 (NEP25) transgenic (Tg) mice.
Methods
At 8 weeks of age, male NEP25 Tg mice were injected with LMB2 at a dose of 0.9 ng/g body weight. Throughout the study, mice had free access to standard mouse chow or modified AIN93G purified diet. All experiments were conducted with n=3–5, and each experiment was repeated at least three times.
Results
Under standard diet conditions, LMB2-treated mice developed proteinuria and glomerulosclerosis. While plasma phosphate (Pi) and parathyroid hormone (PTH) levels remained unchanged compared to non-treated controls, fibroblast growth factor 23 (FGF23) levels were significantly elevated. In contrast, under the AIN93G diet, LMB2-treated mice exhibited significant increases in plasma Pi, PTH, and FGF23 levels. Furthermore, under the AIN93G diet, micro-computed tomography analysis revealed marked reductions in bone mineral density and deterioration of trabecular architecture in both cortical and cancellous bone compartments in LMB2-treated mice. Furthermore, under standard dietary conditions, the expression of FGF23 and FAM20C mRNA in bone was not significantly altered, whereas GALNT3 expression was significantly upregulated. Under the AIN93G diet, however, LMB2 treatment resulted in a significant upregulation of FGF23, FAM20C, and GALNT3 mRNA expression in the bone.
Conclusion
These results indicate that NEP25 transgenic mice constitute a relevant and reliable model for elucidating the pathophysiological mechanisms of the CKD-MBD model.
Funding
- Government Support – Non-U.S.