Kbus/Idr, a mutant mouse strain with skeletal abnormalities and hypophosphatemia: Identification as an allele of 'Hyp'

Journal of Biomedical Science

Research

Atsuko Hanai¹  Kenji Moriyama²  Kazuyuki Mekada³  Atsushi Yoshiki³  Takayuki Takahashi⁴  Katsueki Ogiwara⁴  Atsushi Kimura⁴ 

[1] Department of Developmental Biology, Institute for Developmental Research, Aichi Human Service Center, 487-0392, Kasugai, Japan;Department of Medicine & Clinical Science, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 663-8179, Nishinomiya, Japan;Division of Experimental Animal Research, BioResource Center, RIKEN Tsukuba Institute, 305-0074, Tsukuba, Japan;Laboratory of Reproductive and Developmental Biology, Faculty of Science, Hokkaido University, 060-0810, Sapporo, Japan;

关键词: Bone defects;    Hypophosphatemia;    Mouse model;    Phex;    Hyp;    XLH;   

DOI  :  10.1186/1423-0127-18-60

 received in 2011-04-03, accepted in 2011-08-20,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsHistopathological 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.ResultsKbus/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.ConclusionsKbus mice should serve as a useful research tool exploring molecular mechanisms underlying aberrant Phex-associated pathophysiological phenomena.

【 授权许可】

CC BY   
© Moriyama et al; licensee BioMed Central Ltd. 2011