Department of Internal Medicine, Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut.
Department of Nephrology and Hypertension, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Am J Physiol Renal Physiol. 2021 Jun 1;320(6):F1106-F1122. doi: 10.1152/ajprenal.00556.2020. Epub 2021 May 3.
Ksp-cadherin (cadherin-16) is an atypical member of the cadherin superfamily of cell adhesion molecules that is ubiquitously expressed on the basolateral membrane of epithelial cells lining the nephron and the collecting system of the mammalian kidney. The principal aim of the present study was to determine if Ksp-cadherin played a critical role in the development and maintenance of the adult mammalian kidney by generating and evaluating a mouse line deficient in Ksp-cadherin. Ksp-null mutant animals were viable and fertile, and kidneys from both neonates and adults showed no evidence of structural abnormalities. Immunolocalization and Western blot analyses of Na-K-ATPase and E-cadherin indicated that Ksp-cadherin is not essential for either the genesis or maintenance of the polarized tubular epithelial phenotype. Moreover, E-cadherin expression was not altered to compensate for Ksp-cadherin loss. Plasma electrolytes, total CO, blood urea nitrogen, and creatinine levels were also unaffected by Ksp-cadherin deficiency. However, a subtle but significant developmental delay in the ability to maximally concentrate urine was detected in Ksp-null mice. Expression analysis of the principal proteins involved in the generation of the corticomedullary osmotic gradient and the resultant movement of water identified misexpression of aquaporin-2 in the inner medullary collecting duct as the possible cause for the inability of young adult Ksp-cadherin-deficient animals to maximally concentrate their urine. In conclusion, Ksp-cadherin is not required for normal kidney development, but its absence leads to a developmental delay in maximal urinary concentrating ability. Ksp-cadherin (cadherin-16) is an atypical member of the cadherin superfamily of cell adhesion molecules that is ubiquitously expressed on the basolateral membrane of epithelial cells lining the nephron and the collecting system. Using knockout mice, we found that Ksp-cadherin is in fact not required for kidney development despite its high and specific expression along the nephron. However, its absence leads to a developmental delay in maximal urinary concentrating ability.
Ksp-钙黏蛋白（钙黏蛋白-16）是细胞黏附分子钙黏蛋白超家族的一个非典型成员，广泛表达于肾单位和哺乳动物肾脏集合系统衬里的上皮细胞的基底外侧膜上。本研究的主要目的是通过生成和评估缺乏 Ksp-钙黏蛋白的小鼠品系来确定 Ksp-钙黏蛋白是否在成年哺乳动物肾脏的发育和维持中发挥关键作用。Ksp 缺失突变体动物具有活力和繁殖力，新生儿和成年肾脏均未显示出结构异常的证据。Na-K-ATP 酶和 E-钙黏蛋白的免疫定位和 Western blot 分析表明，Ksp-钙黏蛋白对于极化管状上皮表型的发生或维持不是必需的。此外，E-钙黏蛋白的表达没有改变以弥补 Ksp-钙黏蛋白的缺失。Ksp 钙黏蛋白缺乏也不会影响血浆电解质、总二氧化碳、血尿素氮和肌酐水平。然而，在 Ksp 缺失小鼠中，尿液浓缩能力的最大能力发展出现了微妙但显著的延迟。参与皮质髓质渗透梯度生成和水运动的主要蛋白的表达分析表明，内髓集合管中水通道蛋白-2的表达异常可能是年轻成年 Ksp 钙黏蛋白缺乏动物无法最大程度浓缩尿液的原因。总之，Ksp-钙黏蛋白不是正常肾脏发育所必需的，但它的缺失会导致最大尿液浓缩能力的发育延迟。
