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The Role of MUC1 in Lactation‐Associated Bone Mineral Conservation
Author(s) -
Ray Evan C.,
AlBataineh Mohammad,
Lam Tracey,
Kinlough Carol C.,
Marciszyn Allison L.,
Barbour Jenna,
Tourkova Irina,
Blair Harry C.,
Kleyman Thomas R.,
Hughey Rebecca P.
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r3809
Subject(s) - lactation , endocrinology , medicine , bone mineral , hypomagnesemia , kidney , excretion , duodenum , urinary system , chemistry , biology , osteoporosis , pregnancy , genetics , organic chemistry , magnesium
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 Ca 2+ and Mg 2+ ‐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 Mg 2+ and with differences in bone density. We observe that MUC1 ‐/‐ animals exhibit hypomagnesemia, but only mild reduction in blood Ca 2+ , and no change in daily urinary Ca 2+ or Mg 2+ 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 Ca 2+ and Mg 2+ during lactation. We find that lactating females have reduced blood Ca 2+ and increased urinary Mg 2+ 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 Ca 2+ and Mg 2+ during lactation, an extreme physiologic stressor requiring conservation of these minerals.