Malabsorption of phosphate by the intestines of young X-linked hypophosphatemic mice

Summary

X-linked hypophosphatemic (Hyp) mice are a model for human X-linked (familial) hypophosphatemia (vitamin D-resistant rickets). In several studies, Hyp mice have been shown to exhibit either normal intestinal phosphate absorption or malabsorption of phosphate. These apparently conflicting reports led us to further investigate intestinal phosphate absorption. Isolated intestinal segmentsin vivo were used in C57BL/6J normal and Hyp mice, both male and female.³³P was placed in the segment in 2 mM Na₂HPO₄+150 mM NaCl, pH 7.2. Mice at 4, 7, and 12 weeks of age were used. No significant differences in phosphate absorption were found between the sexes. At 4 weeks of age, Hyp mice showed significant malabsorption of phosphate, with the jejunum being the most severely affected. Malabsorption was judged by significantly more³³P remaining in the lumen, less in the intestinal tissue, and less in the plasma. At 7 weeks of age, these same trends were seen but at a nonsignificant level. By the 12th week of life, the absorption of³³P was similar in Hyp and normal mice. Thus, phosphate malabsorption in Hyp mice is an age-related phenomena. These changes parallel the malabsorption of calcium in young Hyp mice and reflect the lowered plasma 1,25-dihydroxyvitamin D (1,25(OH)₂D) levels of young Hyp mice.