Disease relevance of Gy

• Hyp and Gy mice both have X-linked hypophosphatemic rickets, although genetic data and the different phenotypic spectra observed have previously suggested that two different genes are mutated [1].
• An X-linked dominant mutation (gyro, gene symbol Gy) in the laboratory mouse causes hypophosphatemia, rickets/osteomalacia, circling behavior, inner ear abnormalities, and sterility in males and a milder phenotype in females [2].
• Malabsorption of calcium in young Gy and Hyp mice may exacerbate the low mineralization in their rachitic bone disease [3].
• X-linked hypophosphatemia, a common metabolic bone disease in humans and mice (the Hyp and Gy mutations), is characterized by decreased plasma phosphate, decreased renal tubular reabsorption of phosphate, rickets, and osteomalacia [3].
• Craniofacial abnormalities in mice with X-linked hypophosphatemic genes (Hyp or Gy) [4].

High impact information on Gy

• Following whole body gamma-irradiation (8 Gy) mutant mice died rapidly from acute radiation toxicity to the small intestine [5].
• Gy and Hyp genes have similar quantitative expression in serum phosphorus values, renal excretion of phosphate, and impairment of Na+/phosphate cotransport by renal brush-border membrane vesicles [2].
• Gy maps closely (crossover value 0.4-0.8%) to another X-linked gene (Hyp) that also causes hypophosphatemia in the mouse [2].
• Spermine deficiency in Gy mice caused by deletion of the spermine synthase gene [6].
• To elucidate the complex phenotype of Gy mice, we characterized the genomic region upstream of Phex [6].

Biological context of Gy

• In Gy mice, the first three exons and the promotor region are deleted [1].
• Following the 4 week study, intestinal absorption was measured at 2, 7-8, and 12 weeks of age in normal and Gy mice on the B6C3H background [3].
• This depletion, which included spermine deficiency, dramatically increased caspase activation and cell death in Gy fibroblasts exposed to UV irradiation [7].
• Two closely linked hypophosphatemic genes, hypophosphatemia (Hyp) and Gyro (Gy), are known on the mouse X chromosome [8].
• Gy provides a mouse model for a defect in the polyamine pathway, which is known to play a key role in cell proliferation [6].

Anatomical context of Gy

• However, when compared with fibroblasts obtained from normal male littermates (N cells), Gy fibroblasts were observed to grow normally [7].
• I(K1)current densities were not altered in Gy myocytes, but the steepness of rectification was reduced indicating a role for spermine in controlling rectification [9].
• The present results demonstrate that hypophosphatemia in Gy mice can be attributed to a decrease in the maximum velocity of the high affinity Na(+)-phosphate cotransport process in renal brush-border membranes [10].

Associations of Gy with chemical compounds

• Serum 1,25-dihydroxyvitamin D was not significantly altered in Gy males at 4 weeks of age [3].
• Gy fibroblasts do not contain spermine and have a higher spermidine content [7].
• In Gy cells depleted of polyamines by DFMO, polyamine replenishment with either spermidine or spermine was sufficient to restore caspase activity induced by etoposide, indicating that, in this model, polyamines have an interchangeable role in supporting caspase activation [7].
• On the other hand, in either N or Gy cells, DFMO treatment did not influence caspase activity triggered by staurosporine, but inhibited it when the inducers were cycloheximide or etoposide [7].
• Glucose uptake levels in the BBMV were 1.94 +/- 0.87 and 1.91 +/- 0.35 pmol x mg protein-1 x 6 s-1 in normal and Gy mice, respectively (n=3) [11].

Analytical, diagnostic and therapeutic context of Gy

• Western blot analysis of renal BBM proteins, using a polyclonal antiserum, showed one predominant band at 87 kDa in both mouse samples, with intensities being decreased in the Gy mice (normal/Gy=4.129 +/- 0.70, n=4, P< 0.04) [11].
• Two animal models of the human disorder hypophosphatemic vitamin D-resistant rickets exist, the Hyp and Gy mice [11].

References