Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 of 45Ca was measured in isolated duodenal segments in vivo in mice from 2-13 weeks of age. The duodenum was isolated by sutures and 45Ca 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. Hemizygous Hyp male and heterozygous Hyp female mice absorbed significantly less 45Ca at 4 and 7 weeks of age than genetically normal mice while Hyp mice at 2, 10, and 13 weeks of age were not significantly affected. At 4 and 7 weeks of age, the Hyp 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 and Hyp duodenum. There were non-significant differences between the normal and Hyp mice in both binding affinity, Kd, and the number of receptors, nmax. In conclusion, juvenile Hyp mice at 4 and 7 weeks of ages malabsorbed calcium from their duodenum. Hyp mice younger than this period were not affected nor were adult Hyp mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced absorption of 45calcium from isolated duodenal segments in vivo in juvenile but not adult X-linked hypophosphatemic mice. 300 89

X-linked hypophosphatemic (Hyp) mice are a model for human sex-linked vitamin D-resistant rickets. We have reported intestinal malabsorption of calcium in young Hyp mice, and in this report we have explored the mechanism for it. To test for resistance of the intestine to 1,25(OH)2 vitamin D3, this hormone was continually infused via osmotic minipumps into 4-week-old normal and Hyp mice at 0, 17, 50 or 150 ng/kg/day. After 3 days, 45Ca and inorganic 32P were administered by gavage, and the mice were sacrificed on the fifth day. The Hyp mice showed responses to the hormone equivalent to the normal mice in terms of increased intestinal absorption of both 45Ca and 32P, increased plasma isotope levels, increased femoral isotope content, and increased duodenal and renal 9 kD vitamin D-dependent calcium-binding protein (calbindin-D9K; CaBP). Plasma 1,25(OH)2D was measured in these mice. There were significant correlations of plasma 1,25(OH)2D to the intestinal absorption of 45Ca and 32P and to duodenal and renal CaBP. Plasma 1,25(OH)2D was also measured in stock normal and Hyp mice and was found to be lower in 4-week-old Hyp mice than in 4-week-old normal mice (113 +/- 10 pM (n = 18) vs. 67 +/- 10 (n = 20), normal vs. Hyp, p less than .01), but unchanged at 13 weeks of age (77 +/- 13 (n = 13) vs. 70 +/- 15 (n = 15), NS). This observed difference in plasma 1,25(OH)2D between normal and Hyp mice at 4 weeks of age was sufficient to explain the observed normal-to-Hyp differences in intestinal absorption of 45Ca and duodenal and renal CaBP. It also explained 72 +/- 18% of the observed difference in 32P absorption. We conclude that Hyp mouse intestine is not resistant to 1,25(OH)2D and that the lower plasma 1,25(OH)2D of 4-week-old Hyp mice causes intestinal malabsorption of calcium and phosphate.
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PMID:Evidence that low plasma 1,25-dihydroxyvitamin D causes intestinal malabsorption of calcium and phosphate in juvenile X-linked hypophosphatemic mice. 345 58

Low duodenal vitamin D-dependent calcium-binding protein has been reported in juvenile Hyp mice. Levels of this protein improved in adult Hyp mice. This led to the search for possible abnormal intestinal calcium absorption in juvenile Hyp mice and for evidence that calcium malabsorption, if present, would exacerbate the bone disease. A balance study was performed in 10 sets of normal and Hyp male mice at 5 and 12 weeks of age. Twelve-week-old Hyp mice had balances (24-h intake minus excretion) of Ca, P, Mg, Na, and K that were not significantly different from those of 12-week-old normal mice. However, 5-week-old Hyp mice had a significantly lower balance of Ca with higher fecal Ca and lower urinary Ca. No balance was also lower due to higher fecal Na. The balances of P, Mg, and K were not significantly affected in young Hyp mice. Growth and mineralization of the femur were compared in normal and heterozygous female Hyp mice from 3.5-46 weeks of age. The femora of Hyp mice gained ash weight at a rate comparable to that for normal mice, except for a lag between 3.5 and 7 weeks. There was life-long hypophosphatemia and elevated plasma alkaline phosphatase. It was concluded that the period of low levels of duodenal vitamin D-dependent calcium-binding protein was associated with low intestinal absorption and low skeletal mineralization. This dysfunction of the intestine in juvenile, rapidly growing Hyp mice may exacerbate the bone disease.
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PMID:A role for the intestine in the bone disease of juvenile X-linked hypophosphatemic mice: malabsorption of calcium and reduced skeletal mineralization. 609 Jan 1