The Role of MUC1 in Lactation‐Associated Bone Mineral Conservation

Abstract

To provide bone minerals to nursing offspring, lactating females dramatically up‐regulate their own renal and gastrointestinal transport processes to maximize conservation of these minerals. This includes increased expression of Ca2+ and Mg2+‐selective Trp channels in the kidney’s distal convoluted tubule (DCT) and in the duodenum. The transmembrane glycoprotein, Mucin 1 (MUC1) is expressed in both of these epithelia and interacts with Trp channels, enhancing apical localization of the channels in vivo. Human polymorphisms in MUC1 are associated with altered blood Mg2+ and with differences in bone density. We observe that MUC1‐/‐ animals exhibit hypomagnesemia, but only mild reduction in blood Ca2+, and no change in daily urinary Ca2+ or Mg2+ excretion, in spite of reduced apical localization of TrpV5 in the kidney’s DCT, and TrpV6 in the duodenum. We hypothesized that MUC1‐/‐ dams would exhibit reduced ability to conserve Ca2+ and Mg2+ during lactation. We find that lactating females have reduced blood Ca2+ and increased urinary Mg2+ concentrations compared to wild‐type lactating dams. Additionally, pups from MUC1‐/‐ dams exhibit reduced bone mineral density compared to pups from control dams. These findings suggest an important role for MUC1 in minimizing excretion of Ca2+ and Mg2+ during lactation, an extreme physiologic stressor requiring conservation of these minerals.