Reduced absorption of⁴⁵calcium from isolated duodenal segmentsin vitro in juvenile but not adult X-linked hypophosphatemic mice

Summary

In juvenile X-linked hypophosphatemic (Hyp) mice, whole body calcium balances are significantly lower than in genetically normal mice. This is associated with low duodenal vitamin D-dependent calcium-binding protein and a failure of skeletal mineralization. To seek more specific evidence of an intestinal defect in these mice, absorption of⁴⁵Ca was measured in isolated duodenal segmentsin vivo in mice from 2–13 weeks of age. The duodenum was isolated by sutures and⁴⁵Ca was injected into the lumen in 150 mM NaCl and 2 mM CaCl₂ at pH=7.2. Absorption was measured by the amount of isotope remaining in the lumen and by the plasma isotope level. HemizygousHyp male and heterozygousHyp female mice absorbed significantly less⁴⁵Ca at 4 and 7 weeks of age than genetically normal mice whileHyp mice at 2, 10, and 13 weeks of age were not significantly affected. At 4 and 7 weeks of age, theHyp mice also had significantly reduced plasma radioactivity midway through the collection period as well as at the end of the period. To explore a possible mechanism for this malabsorption, 1,25(OH)₂-vitamin D receptors were measured in cytosol prepared from 4-week-old normal andHyp duodenum. There were non-significant differences between the normal andHyp mice in both binding affinity, K_d, and the number of receptors, n_max. In conclusion, juvenileHyp mice at 4 and 7 weeks of ages malabsorbed calcium from their duodenum.Hyp mice younger than this period were not affected nor were adultHyp mice. This delay in the development of calcium absorption was not caused by a delay in the appearance of intestinal receptors for 1,25(OH)₂D.