Fox J, Maunder E M, Randall V A, Care A D
Clin Sci (Lond). 1985 Nov;69(5):541-8. doi: 10.1042/cs0690541.
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.
我们培育出了一种患有遗传性低钙血症佝偻病的猪种，其遗传机制为常染色体隐性遗传。纯合子（患病）仔猪的生长速度仅为其杂合子（临床正常）同窝仔猪的一半，到8周龄时会出现严重的低钙血症，并伴有严重的继发性甲状旁腺功能亢进和低磷血症。在低钙血症仔猪中，血浆1,25 - 二羟维生素D水平较低或检测不到，尽管25 - 羟维生素D3水平高出2倍，但24,25 - 二羟维生素D3水平也降低。从患病动物制备的肾匀浆中未检测到25 - 羟维生素D3 - 1 - 或 - 24 - 羟化酶活性。低钙血症仔猪的血浆和肠道钙结合蛋白水平降低。在高盐缓冲液中制备的肠道细胞溶质的蔗糖密度梯度分析显示，两组仔猪中存在相似数量的特定的小于4.2S的1,25 - 二羟维生素D3结合物。给患病动物注射药理剂量的维生素D3可逆转低钙血症。我们得出结论，这种猪种患有I型维生素D依赖性佝偻病。
