Panda D K, Al Kawas S, Seldin M F, Hendy G N, Goltzman D
Calcium Research Laboratory, Royal Victoria Hospital, Montreal, Quebec, Canada.
J Bone Miner Res. 2001 Jan;16(1):46-56. doi: 10.1359/jbmr.2001.16.1.46.
The murine homologue of the 25-hydroxyvitamin D [25(OH)D] 1alpha-hydroxylase gene [1alpha(OH)ase; Cyp27bl], which is mutated in humans with vitamin D-dependent rickets type I (VDDR-I; also known as pseudovitamin D-deficiency rickets [PDDR]) was cloned and characterized. Like the human, the mouse gene has nine exons, and the exon-intron organization is well conserved. By interspecific backcross analysis, the Cyp27bl gene was mapped to 70.5 cM on mouse Chr 10. This is in a region syntenic with human Chr 12q13.1-q13.3 to which the human 1alpha(OH)ase gene was previously mapped. Kidney expression of the 1alpha(OH)ase was localized to cortical tubules and was higher in the adult mouse than in the fetus, consistent with the increased role of its product as a circulating hormone postnatally. Prenatally, the 1alpha(OH)ase gene, together with the vitamin D receptor (VDR) gene, was expressed in embryonic stem cells, and expression of 1alpha(OH)ase in bone and intestine was higher in the fetus than in the adult. These observations suggest that 1,25-dihydroxyvitamin D [1,25(OH)2D] plays a role in fetal development. In view of the fact that humans lacking 1alpha(OH)ase have apparently normal prenatal development, this may point to functional redundancy in the fetal vitamin D system, which now can be explored further in mouse models in which the 1alpha(OH)ase gene has been deleted.
在患有I型维生素D依赖性佝偻病（VDDR-I；也称为假性维生素D缺乏性佝偻病[PDDR]）的人类中发生突变的25-羟基维生素D [25(OH)D] 1α-羟化酶基因[1α(OH)酶；Cyp27bl]的小鼠同源物被克隆并进行了表征。与人类一样，小鼠基因有9个外显子，外显子-内含子组织高度保守。通过种间回交分析，Cyp27bl基因被定位到小鼠第10号染色体上70.5 cM处。这一区域与人类第12号染色体q13.1-q13.3同线，人类1α(OH)酶基因先前被定位到该区域。1α(OH)酶在肾脏中的表达定位于皮质小管，在成年小鼠中高于胎儿，这与其产物在出生后作为循环激素的作用增加一致。在产前，1α(OH)酶基因与维生素D受体（VDR）基因一起在胚胎干细胞中表达，1α(OH)酶在胎儿骨骼和肠道中的表达高于成年个体。这些观察结果表明，1,25-二羟基维生素D [1,25(OH)2D]在胎儿发育中起作用。鉴于缺乏1α(OH)酶的人类产前发育明显正常，这可能表明胎儿维生素D系统存在功能冗余，现在可以在已删除1α(OH)酶基因的小鼠模型中进一步探索。
