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

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...

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Autores principales: Moriyama, Kenji, Hanai, Atsuko, Mekada, Kazuyuki, Yoshiki, Atsushi, Ogiwara, Katsueki, Kimura, Atsushi, Takahashi, Takayuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175157/
https://www.ncbi.nlm.nih.gov/pubmed/21854633
http://dx.doi.org/10.1186/1423-0127-18-60
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author Moriyama, Kenji
Hanai, Atsuko
Mekada, Kazuyuki
Yoshiki, Atsushi
Ogiwara, Katsueki
Kimura, Atsushi
Takahashi, Takayuki
author_facet Moriyama, Kenji
Hanai, Atsuko
Mekada, Kazuyuki
Yoshiki, Atsushi
Ogiwara, Katsueki
Kimura, Atsushi
Takahashi, Takayuki
author_sort Moriyama, Kenji
collection PubMed
description 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.
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spelling pubmed-31751572011-09-18 Kbus/Idr, a mutant mouse strain with skeletal abnormalities and hypophosphatemia: Identification as an allele of 'Hyp' Moriyama, Kenji Hanai, Atsuko Mekada, Kazuyuki Yoshiki, Atsushi Ogiwara, Katsueki Kimura, Atsushi Takahashi, Takayuki J Biomed Sci Research 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. BioMed Central 2011-08-20 /pmc/articles/PMC3175157/ /pubmed/21854633 http://dx.doi.org/10.1186/1423-0127-18-60 Text en Copyright ©2011 Moriyama et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Moriyama, Kenji
Hanai, Atsuko
Mekada, Kazuyuki
Yoshiki, Atsushi
Ogiwara, Katsueki
Kimura, Atsushi
Takahashi, Takayuki
Kbus/Idr, a mutant mouse strain with skeletal abnormalities and hypophosphatemia: Identification as an allele of 'Hyp'
title Kbus/Idr, a mutant mouse strain with skeletal abnormalities and hypophosphatemia: Identification as an allele of 'Hyp'
title_full Kbus/Idr, a mutant mouse strain with skeletal abnormalities and hypophosphatemia: Identification as an allele of 'Hyp'
title_fullStr Kbus/Idr, a mutant mouse strain with skeletal abnormalities and hypophosphatemia: Identification as an allele of 'Hyp'
title_full_unstemmed Kbus/Idr, a mutant mouse strain with skeletal abnormalities and hypophosphatemia: Identification as an allele of 'Hyp'
title_short Kbus/Idr, a mutant mouse strain with skeletal abnormalities and hypophosphatemia: Identification as an allele of 'Hyp'
title_sort kbus/idr, a mutant mouse strain with skeletal abnormalities and hypophosphatemia: identification as an allele of 'hyp'
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175157/
https://www.ncbi.nlm.nih.gov/pubmed/21854633
http://dx.doi.org/10.1186/1423-0127-18-60
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