title: Vitamin D-dependent rickets type I in pigs.
abstract: We have bred a strain of pigs with an inherited condition of hypocalcaemic rickets, transmitted by an autosomal-recessive mechanism. Homozygous (affected) piglets grew at half the rate of their heterozygous (clinically normal) littermates, and developed profound hypocalcaemia with severe secondary hyperparathyroidism and hypophosphataemia by 8 weeks of age. In the hypocalcaemic piglets, plasma 1,25-dihydroxyvitamin D levels were low or undetectable, and 24,25-dihydroxyvitamin D3 levels were also reduced despite 25-hydroxyvitamin D3 levels being 2-fold higher. There was no detectable 25-hydroxyvitamin D3-1- or -24-hydroxylase enzyme activity in renal homogenates prepared from affected animals. Plasma and intestinal calcium-binding protein levels were reduced in the hypocalcaemic piglets. Sucrose density gradient analysis of intestinal cytosol, prepared in high-salt buffer, revealed the presence of a similar amount of a specific less than 4.2S 1,25-dihydroxyvitamin D3 binder in both groups of piglets. Administration of pharmacological doses of vitamin D3 to affected animals reversed the hypocalcaemia. We conclude that this strain of pigs has vitamin D-dependent rickets type I.
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D002135:Calcium-Binding Proteins / Q000032:analysis; D003577:Cytochrome P-450 Enzyme System; D006996:Hypocalcemia / Q000201:enzymology / Q000378:metabolism; D007015:Hypophosphatemia, Familial / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D013250:Steroid Hydroxylases / Q000378:metabolism; D013552:Swine; D014807:Vitamin D / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D002135:Calcium-Binding Proteins; D014807:Vitamin D; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase