Journal Article

Genetic deletion of connexin 37 causes polyuria and polydipsia

Xue, Jianxiang, Rieg, Timo, Dominguez Rieg, Jessica A., Thomas, Linto, Fenton, Robert A.

2020

Overview

The connexin 37 (Cx37) channel is clustered at gap junctions between cells in the renal vasculature or the renal tubule where it is abundant in basolateral cell interdigitations and infoldings of epithelial cells in the proximal tubule, thick ascending limb, distal convoluted tubule and collecting duct; however, physiological data regarding its role are limited. In this study, we investigated the role of Cx37 in fluid homeostasis using mice with a global deletion of Cx37 (Cx37 -/- mice). Under baseline conditions, Cx37 -/- had ~40% higher fluid intake associated with ~40% lower urine osmolality compared to wild-type (WT) mice. No differences were observed between genotypes in urinary adenosine triphosphate or prostaglandin E2, paracrine factors that alter renal water handling. After 18-hours of water deprivation, plasma aldosterone and urine osmolality increased significantly in Cx37 -/- and WT mice; however, the latter remained ~375 mmol/kg lower in Cx37 -/- mice, an effect associated with a more pronounced body weight loss despite higher urinary AVP/creatinine ratios compared to WT mice. Consistent with this, fluid intake in the first 3 hours after water deprivation was 37% greater in Cx37 -/- vs WT mice. Cx37 -/- mice showed significantly lower renal AQP2 abundance and AQP2 phosphorylation at serine 256 than WT mice in response to vehicle or dDAVP, suggesting a partial contribution of the kidney to the lower urine osmolality. The abundance and responses of the vasopressin V 2 receptor, AQP3, NHE3, NKCC2, NCC, H + -ATPase, αENaC, γENaC or Na + /K + -ATPase were not significantly different between genotypes. In summary, these results demonstrate that Cx37 is important for body water handling.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenosine triphosphate / Aldosterone / Animals / Aquaporin 2 / Aquaporin 2 - genetics / Aquaporin 2 - metabolism / Aquaporin 3 / ATP / Biology and Life Sciences / Body water / Body weight / Body weight loss / Causes of / Cellular proteins / Collecting duct / Connexins - physiology / Creatinine / Deletion / Enzymes / Epithelial cells / Female / Fluid intake / Gap Junction alpha-4 Protein / Gap junctions / Gene Deletion / Genetic aspects / Genotypes / H+-transporting ATPase / Homeostasis / Kidneys / Laboratory animals / Male / Medical schools / Medicine / Medicine and Health Sciences / Mice / Mice, Inbred C57BL / Mice, Knockout / Mutation / Na+/K+-exchanging ATPase / Paracrine signalling / Pharmacology / Phosphorylation / Physical Sciences / Physiology / Plasma / Polydipsia / Polydipsia - etiology / Polydipsia - pathology / Polyuria - etiology / Polyuria - pathology / Proteins / Renal function / Salt / Urination disorders / Urine / Vasopressin / Water deprivation / Weight loss