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

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.During the maintenance of the KYF/MsIdr strain of mouse, which earlier spontaneously yielded an abnormal behavior-displaying Usher-1D model, BUS/Idr [1,2], we recognized the occurrence of dwarfism-like short-tailed individuals, which displayed distinct bustling behavior. We have established the mutant as a new strain, Kbus/Idr, through brother-sister mating, and attempted to specify the responsible gene(s), as dealt with in this paper.Osteogenesis is controlled by osteoblast/osteoclast functional balance in close association with phosphate (Pi) homeostasis regulated by complicated systems operating across the parathyroid gland, intestine, bone and kidney [3,4]. Parathyroid hormone (PTH), 1,25-vitamin D3 and calcium-sensing receptors constitute the classic pathway of Pi/calcium homeostasis, which is essential for bone differentiation and remodeling. In addition, two important key mediators have been identified through clinical observation and subsequent molecular approaches, fibroblast growth factor-23 (FGF23) and a phosphate-regulating gene product with homology to endopeptidases linked to the X chromosome (PHEX). Gain-of-function mutations of FGF23 lead to autosomal dominant h