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

Abstract

Summary.A new genetic mutant in mice, Hyp, has been proposed as a model for the human disease Xlinked hypophosphatemia (the most common form of vitamin D-resistant rickets). The gene is Xlinked, 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 hemizygous Hyp male mice were compared with their normal lfttermate controls. The Hyp 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 the Hyp mice, showed no striking alternations in inorganic or total phosphate content, dry weight (as % wet weight), or extracellular fluid space. The Hyp gene in mice seems to produce a condition similar to that of X-linked hypophosphatemia in humans.Send offprint requests to Ralph A. Meyer, Jr., at the above address.

Healing of rickets with phosphate supplementation in the hypophosphatemic male mouse.

“…As in the human disease, the mutation is transmitted as an X-linked dominant trait and causes hypophosphatemia due to an intrinsic renal tubular reabsorption defect for phosphate (2). Moreover, the Hyp mouse has a mild hypocalcemia (1) and reduced bone magnesium (Mg) content (3). Besides these biochemical abnormalities, the mutant animal presents with growth retardation resulting from rickets (1) and skeletal deformities associated with histologic evidence of osteomalacia (3).…”

“…Moreover, the Hyp mouse has a mild hypocalcemia (1) and reduced bone magnesium (Mg) content (3). Besides these biochemical abnormalities, the mutant animal presents with growth retardation resulting from rickets (1) and skeletal deformities associated with histologic evidence of osteomalacia (3). In children with VDRR, the radiological appearance of rickets can be healed by adequate supplementation of phosphate (Pi) (4) whereas osteomalacia remains uncured (5,6).…”

Isoproterenol Increases Renal Tubular Reabsorption of Phosphate in X-Linked Hypophosphatemic (<i>Hyp</i>) Mice

“…tively, and tap water ad libitum. The mice were weaned at 3 weeks of age, at which time mutant mice were identified by low plasma Statistics phosphate levels, low body weight, and short tails [15].…”

Humoral Abnormalities in X-Linked Hypophosphatemic Mice

“…In both species there is reduced renal tubular reabsorption of phosphate, hypophosphatemia and a rachitic or osteomalacic bone disease [1][2][3]. In children in this country it is judged the most common metabolic bone disease [I], The mutant gene in mice is known as Hyp.…”