- 作者: Kenji Moriyama; Atsuko Hanai; Kazuyuki Mekada; Atsushi Yoshiki; Katsueki Ogiwara; Atsushi Kimura; Takayuki Takahashi
- 作者服務機構: Department of Medicine & Clinical Science, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women’s University, Japan
- 中文摘要: --
- 英文摘要:
Background: 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.
Methods: 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.
Results: 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.
Conclusions: Kbus mice should serve as a useful research tool exploring molecular
mechanisms underlying aberrant Phex-associated pathophysiological phenomena. - 中文關鍵字: --
- 英文關鍵字: Bone defects, Hypophosphatemia, Mouse model, Phex, Hyp, XLH