Slc34a1, encoding renal sodium-phosphate cotransporter 2A (NaPi-IIa), is crucial for maintaining phosphate homeostasis in the kidneys. It is involved in the reabsorption of phosphate from the renal tubules, and this process is associated with calcium and vitamin D metabolism pathways, which are essential for normal physiological function [1,2]. Genetic models, such as knockout mouse models, are valuable tools for studying its functions.

Analysis of calcium and phosphate metabolism in Slc34a1-knockout mice highlighted that phosphate depletion and fibroblast growth factor-23 suppression due to defective NaPi-IIa function can lead to inappropriate production of 1,25-(OH)2D3, resulting in symptomatic hypercalcemia, as seen in idiopathic infantile hypercalcemia (IIH) [1]. Also, patients with biallelic SLC34A1 variant carriers showed polyuria, failure to thrive, vomiting, constipation, hypercalcemia and nephrocalcinosis in infancy, and an attenuation of clinical features was observed after infancy, independent of treatment [3].

In conclusion, Slc34a1 is essential for phosphate reabsorption in the kidneys and maintaining calcium and phosphate homeostasis. The study of Slc34a1 knockout mouse models has revealed its key role in the development of IIH and related disorders, providing important insights into the underlying mechanisms of these diseases [1,3].

References:

1. Schlingmann, Karl P, Ruminska, Justyna, Kaufmann, Martin, Wagner, Carsten A, Konrad, Martin. 2015. Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia. In Journal of the American Society of Nephrology : JASN, 27, 604-14. doi:10.1681/ASN.2014101025. https://pubmed.ncbi.nlm.nih.gov/26047794/

2. De Paolis, Elisa, Scaglione, Giovanni Luca, De Bonis, Maria, Minucci, Angelo, Capoluongo, Ettore. . CYP24A1 and SLC34A1 genetic defects associated with idiopathic infantile hypercalcemia: from genotype to phenotype. In Clinical chemistry and laboratory medicine, 57, 1650-1667. doi:10.1515/cclm-2018-1208. https://pubmed.ncbi.nlm.nih.gov/31188746/

3. Brunkhorst, Max, Brunkhorst, Lena, Martens, Helge, Emma, Francesco, Haffner, Dieter. 2024. Presentation and outcome in carriers of pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter NPT 2a and 2c. In Kidney international, 107, 116-129. doi:10.1016/j.kint.2024.08.035. https://pubmed.ncbi.nlm.nih.gov/39461557/