Meyer R A, Tenenhouse H S, Meyer M H, Klugerman A H
Department of Basic Sciences, School of Dentistry, Marquette University, Milwaukee, WI 53233.
J Bone Miner Res. 1989 Aug;4(4):523-32. doi: 10.1002/jbmr.5650040411.
The X-linked hypophosphatemic (Hyp) mouse is a model for human X-linked hypophosphatemia. Surgical joining of normal to Hyp mice by parabiosis results in the normal mice developing low renal retention of phosphate and hypophosphatemia. These results suggest a humoral component to the renal defect. To test whether this component could be parathyroid hormone, surgical parathyroidectomy (PTX) or sham surgery was performed in mice 3 weeks after parabiotic union (n greater than 20 per group). After an overnight fast, PTX mice were hypocalcemic and hyperphosphatemic relative to sham-operated control mice. PTX normal mice joined to PTX Hyp mice were significantly lower in plasma phosphate and higher in fractional excretion of phosphate [U/P phosphate/(U/P creatinine)] when compared with PTX normal mice joined to other PTX normals. To test for more specific evidence of altered renal transport function, renal brush-border membrane vesicles (BBMV) were prepared from these mice, and phosphate and glucose uptakes were measured. The phosphate/glucose transport ratio was lower in BBMV from Hyp mice, joined to either normal mice or to Hyp mice, when compared with that from normal-normal pairs. Moreover, BBMV from normal mice joined to Hyp mice had a significantly lower phosphate/glucose uptake ratio than BBMV from normal mice joined to other normal mice, and their activity approached that of BBMV derived from Hyp mice. Glucose uptake in BBMV was unaffected by parabiosis or genotype. In summary, parabiosis of normal mice to Hyp mice resulted in the development of phosphaturia and decreased BBMV phosphate transport in the normal mice. The persistence of the phosphate transport defect in parathyroidectomized mice suggests that parathyroid hormone is not the humoral factor contributing to these results.
X连锁低磷血症（Hyp）小鼠是人类X连锁低磷血症的一种模型。通过联体生活将正常小鼠与Hyp小鼠手术连接，会导致正常小鼠出现肾脏对磷酸盐的保留能力降低和低磷血症。这些结果提示肾脏缺陷存在一种体液成分。为了检测该成分是否可能是甲状旁腺激素，在联体生活3周后的小鼠中进行了手术甲状旁腺切除术（PTX）或假手术（每组n大于20只）。禁食过夜后，与假手术对照组小鼠相比，PTX小鼠出现低钙血症和高磷血症。与与其他PTX正常小鼠连接的PTX正常小鼠相比，与PTX Hyp小鼠连接的PTX正常小鼠血浆磷酸盐水平显著降低，磷酸盐排泄分数[尿/血磷酸盐/（尿/血肌酐）]升高。为了寻找肾脏转运功能改变的更具体证据，从这些小鼠制备了肾刷状缘膜囊泡（BBMV），并测量了磷酸盐和葡萄糖的摄取。与正常-正常配对小鼠相比，与正常小鼠或Hyp小鼠连接的Hyp小鼠的BBMV中磷酸盐/葡萄糖转运比值较低。此外，与其他正常小鼠连接的正常小鼠的BBMV相比，与Hyp小鼠连接的正常小鼠的BBMV的磷酸盐/葡萄糖摄取比值显著降低，其活性接近源自Hyp小鼠的BBMV。联体生活或基因型对BBMV中的葡萄糖摄取没有影响。总之，正常小鼠与Hyp小鼠联体生活导致正常小鼠出现磷酸盐尿和BBMV磷酸盐转运减少。甲状旁腺切除小鼠中磷酸盐转运缺陷的持续存在表明甲状旁腺激素不是导致这些结果的体液因子。
