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Osteomalacia and altered magnesium metabolism in the X-linked hypophosphatemic mouse

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Summary

A new genetic mutant in mice,Hyp, has been proposed as a model for the human disease X-linked hypophosphatemia (the most common form of vitamin D-resistant rickets). The gene is X-linked, dominant, and produces reduced renal tubular reabsorption of phosphate, hypophosphatemia, and dwarfism. Our goal was to evaluate the skeletal changes histologically and to measure chemically the prominant blood and bone minerals to judge the suitability of this mutant as a model for the human disease. Thirteen-week-old hemizygousHyp male mice were compared with their normal littermate controls. TheHyp mice were hypocalcemic, hypophosphatemic, hypermagnesemic, and had elevated plasma alkaline phosphatase. The femur ash weighed less than half the normal ash weight but had a normal Ca:P ratio. The ash composition was high in %Na and K but low in %Mg. The mandibular incisor ash was also low in %Mg. Histologically the femur showed wide osteoid borders and wide epiphyseal plate. Microradiography revealed reduced bone density and enlarged osteocyte lacunae. Skeletal muscle samples, although smaller in theHyp mice, showed no striking alternations in inorganic or total phosphate content, dry weight (as % wet weight), or extracellular fluid space. TheHyp gene in mice seems to produce a condition similar to that of X-linked hypophosphatemia in humans.

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Authors and Affiliations

  1. Department of Basic Science, School of Dentistry, Marquette University, 604 North 16th Street, 53233, Milwaukee, Wisconsin, USA

    Ralph A. Meyer Jr. & Martha H. Meyer

  2. Orthopaedic Research, Mayo Clinic, 55901, Rochester, Minnesota, USA

    Jenifer Jowsey

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  1. Ralph A. Meyer Jr.
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  2. Jenifer Jowsey
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  3. Martha H. Meyer
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Meyer, R.A., Jowsey, J. & Meyer, M.H. Osteomalacia and altered magnesium metabolism in the X-linked hypophosphatemic mouse. Calcif Tissue Int 27, 19–26 (1979). https://doi.org/10.1007/BF02441156

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  • DOI: https://doi.org/10.1007/BF02441156

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