Department of Medicine & Clinical Science, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
J Biomed Sci. 2011 Aug 20;18(1):60. doi: 10.1186/1423-0127-18-60.
The endopeptidase encoded by Phex (phosphate-regulating gene with homologies to endopeptidases linked to the X chromosome) is critical for regulation of bone matrix mineralization and phosphate homeostasis. PHEX has been identified from analyses of human X-linked hypophosphatemic rickets and Hyp mutant mouse models. We here demonstrated a newly established dwarfism-like Kbus/Idr mouse line to be a novel Hyp model.
Histopathological and X-ray examination with cross experiments were performed to characterize Kbus/Idr. RT-PCR-based and exon-directed PCR screening performed to identify the presence of genetic alteration. Biochemical assays were also performed to evaluate activity of alkaline phosphatase.
Kbus/Idr, characterized by bone mineralization defects, was found to be inherited in an X chromosome-linked dominant manner. RT-PCR experiments showed that a novel mutation spanning exon 16 and 18 causing hypophosphatemic rickets. Alkaline phosphatase activity, as an osteoblast marker, demonstrated raised levels in the bone marrow of Kbus/Idr independent of the age.
Kbus mice should serve as a useful research tool exploring molecular mechanisms underlying aberrant Phex-associated pathophysiological phenomena.
由 Phex（与 X 染色体相连的内肽酶同源的磷酸调节基因）编码的内肽酶对于调节骨基质矿化和磷酸盐稳态至关重要。PHEX 已从人类 X 连锁低磷酸血症佝偻病和 Hyp 突变小鼠模型的分析中得到鉴定。我们在此证明了新建立的 dwarfism-like Kbus/Idr 小鼠系是一种新型 Hyp 模型。
通过组织病理学和 X 射线检查进行交叉实验，以表征 Kbus/Idr。进行基于 RT-PCR 的和外显子定向 PCR 筛选，以鉴定遗传改变的存在。还进行了生化测定以评估碱性磷酸酶的活性。
Kbus/Idr 表现出骨矿化缺陷，呈 X 染色体连锁显性遗传方式。RT-PCR 实验表明，一种新的突变跨越外显子 16 和 18，导致低磷酸血症佝偻病。碱性磷酸酶活性作为成骨细胞标志物，在 Kbus/Idr 的骨髓中独立于年龄而升高。
Kbus 小鼠应作为探索与异常 Phex 相关的病理生理现象的分子机制的有用研究工具。
