Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0205700 (ash)
 15,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We introduced rat ornithine transcarbamylase (OTC) gene into OTC-deficient spf-ash mice by mating spf-ash heterozygotes with transgenic mice which carried recombinant DNA composed of 1.3 kb of the 5' flanking region of the gene fused onto rat OTC cDNA. The liver OTC activity of hemizygous spf-ash mice which carried the transgene was about twice that of nontransgenic spf-ash mice, and the small intestinal OTC activity was 6 times higher; the values being 12% and 27% of the control levels, respectively. The transgenic spf-ash mice showed normal hair growth without sparse fur, nearly normalized urinary orotic acid excretion and normalized serum citrulline concentration.
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PMID:Correction of ornithine transcarbamylase (OTC) deficiency in spf-ash mice by introduction of rat OTC gene. 200 30

Mutant mice of the Spf-ash strain have an inherited defect in ornithine transcarbamylase (OTC) protein synthesis, and were used to ascertain the potential of recombinant adenoviruses for introducing and expressing the normal gene lacking in these mice. These OTC mutant mice are characterized by a reduction in the amount of OTC activity, resulting in hyperammonemia, pronounced orotic aciduria, growth retardation, and sparse fur until weaning. A recombinant adenovirus that harbors the rat OTC cDNA under the control of the viral major late promoter (MLP) was constructed and injected into such newborn mice. The effect of the virus was analyzed by monitoring the hepatic OTC enzyme during several months after the injection. An increase in OTC activity was detected and was accompanied by a diminution of orotic acid in the urine. The observation of MLP-OTC mRNA transcripts over 1 year following the injection attests to the relatively long-term presence of the transferred gene. In those mice showing the greatest OTC activity, a normalization of the fur was also observed. The experiments reported here document the feasibility of using adenovirus for the direct delivery in vivo of a gene to restore an impaired metabolism.
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PMID:Evaluation of the transfer and expression in mice of an enzyme-encoding gene using a human adenovirus vector. 208 Nov 92

Since the deficiency of ornithine carbamoyltransferase (OCT) is inherited as an X-linked dominant trait in sparse-fur with abnormal skin and hair (Spf-ash) mice, the livers of heterozygous Spf-ash females show mosaicism in regard to OCT. We induced enzyme-altered foci and nodules, presumptive preneoplastic lesions for hepatocellular carcinomas, in the livers of OCT mosaic mice (Spf-ash x C3H F1), and investigated the clonality of the lesions. Simultaneous histochemical staining for OCT and gamma-glutamyl transpeptidase (GGT) demonstrated that all GGT-positive lesions (ranging in size from 3 cells to a few millimeters in diameter) were either positive or negative for OCT, and no mosaic lesions were detectable. The results indicate that individual enzyme-altered hepatocytic lesions are the result of clonal proliferation.
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PMID:Clonal origin of gamma-glutamyl transpeptidase-positive hepatic lesions induced by initiation-promotion in ornithine carbamoyltransferase mosaic mice. 289 63

Laboratory characteristics of a metabolic disease (Osteodystrophia fibrosa) in standard young minks and arctic foxes is described. In comparison with the control group, while the biochemical characteristics of the blood samples of arctic foxes was not very different from the control group in the contents of macroelements (calcium, phosphorus, magnesium), significant differences were revealed by the analyses of the bone samples of os femoris. In young minks the ash weight in 1 g of fat-free dry matter made only 321.94 mg (52.45%), while in the control group 613.82 mg. A similar decrease (P less than 0.01) was observed, in comparison with the control, in the contents of calcium and phosphorus (44.75% and 56.90%). A slight increase in the magnesium content is not statistically significant. Evaluation of ash content in os femoris in young arctic foxes gave similar results. Biochemical characteristics of their blood showed a significant increase in the activity of alkaline phosphatase. An application of the chemical analyses of bones to diagnosing metabolic disturbances in fur animals is discussed.
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PMID:[Changes in the mineral content of bones in fibrous osteodystrophy in standard minks and Arctic foxes]. 308 12

The sparse fur with abnormal skin and hair (Spf-ash) mouse is a model for the human X-linked hereditary disorder, ornithine transcarbamylase (OTC) deficiency. In Spf-ash mice, both OTC mRNA and enzyme activity are 5% of control values resulting in hyperammonemia, pronounced orotic aciduria and an abnormal phenotype characterized by growth retardation and sparse fur. Using microinjection, we introduced a construction containing rat OTC cDNA linked to the SV40 early promoter into fertilized eggs of Spf-ash mice. The expression of the transgene resulted in the development of a transgenic mouse whose phenotype and orotic acid excretion are fully normalized. Thus, the possibility of correcting hereditary enzymatic defect by gene transfer of heterologous cDNA coding for the normal enzyme has been demonstrated.
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PMID:Correction of mouse ornithine transcarbamylase deficiency by gene transfer into the germ line. 316 66

Enzymatic assay, electrophoretic immunoblotting and RNA dot-blot techniques were employed to investigate the expression of the ornithine transcarbamylase (OTC) gene in liver and small intestine of Sparse fur mice with abnormal skin and hair (Spf-ash) and Sparse fur mice (Spf) which exhibit an X-linked OTC deficiency. We found a reduced OTC activity in these two tissues. We now show that this reduction is less pronounced in the intestine than in the liver of the Spf-ash strain. During the first 2 weeks of life, the deficiency appears to be less severe than in the adult mice. The enzymatic activity of carbamylphosphate synthetase I (CPS), another enzyme of the urea cycle, is significantly modified in the Spf mutant strain only.
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PMID:Compared expression levels of ornithine transcarbamylase and carbamylphosphate synthetase in liver and small intestine of normal and mutant mice. 316 57

Seventy-two 3-mo-old pastel mink were fed diets that contained 0, 33, 60, 108, 194 or 350 ppm supplemental fluorine (F), as NaF, for 382 d to assess its effects on growth, fur quality, reproduction and survivability. The basal diet contained 35 ppm F as fed. No significant differences were observed in body weight gains or fur quality between the controls and any of the F-treated groups (P greater than .05). Some males fed 350 ppm supplemental F for a 4-mo period prior to pelting had weakened frontal, parietal and femoral bones that fractured during the pelting process. The F treatments had no measurable adverse effects on breeding, gestation, whelping or lactation, although only 14% of the kits whelped by females fed 350 ppm F survived to 3 wk of age. The survivability of the adult mink was adversely affected only at 350 ppm supplemental F. At the termination of the study, no differences were observed in hematologic parameters or serum calcium concentrations between the controls and treated mink (P greater than .05), but serum alkaline phosphatase activities were increased (P less than .05) by the two highest dietary F levels. Serum F levels were elevated (P less than .01) only in mink fed 194 and 350 ppm F, and urinary and femoral F concentrations in the treated animals were generally greater (P less than .05; P less than .01) than control values and were closely related with dietary F levels. Femoral ash contents of the 194 and 350 ppm F-treated mink were less than the control values (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic toxicity of dietary fluorine to mink. 344 90

Synthesis, mitochondrial transport and processing of ornithine carbamoyltransferase (EC 2.1.3.3) were studied in mutant mice strains (sparse-fur, spf, and sparse-fur with abnormal skin and hair, spf-ash) which exhibit a deficiency in this enzyme. Spf mice have an increased amount (about 150% of control) of the enzyme with abnormal kinetic properties, whereas spf-ash mice have a decreased amount (about 10% of control) of the enzyme with apparently normal kinetic properties. Precursors of the mutant enzymes were synthesized in a reticulocyte lysate cell-free system. The hepatic level of translatable mRNA coding for the enzyme and the rate of the enzyme synthesis in liver slices of spf mice were 58 and 60% of the controls, respectively. In the case of spf-ash mice the activity of translatable mRNA for the enzyme was 10% of the controls. These results indicate that the decreased amount of ornithine carbamoyltransferase protein in spf-ash mice is due mainly to a decreased level of translatable mRNA for the enzyme, whereas the increase in the enzyme amount in spf mice is presumably the result of a decreased rate of enzyme degradation. The subunit molecular weight of the spf enzyme precursor was practically the same as that of the normal enzyme precursor (Mr 40 000). Both precursors synthesized in vitro could be taken up and processed similarly to an apparently mature form (Mr 37 000). In the case of spf-ash enzyme, two discrete in vitro products were observed on sodium dodecyl sulfate polyacrylamide gel; one comigrated with the normal enzyme precursor and the other moved slightly slower. Both products appeared to be taken up and processed to the mature form of the enzyme.
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PMID:Cell-free synthesis and transport of precursors of mutant ornithine carbamoyltransferases into mitochondria. 662 79

We report the effect of the ornithine transcarbamylase (OTC) transgene composed of 1.3 kb of the 5' flanking region of the rat OTC gene fused to rat OTC cDNA on urinary orotic acid excretion in OTC-deficient spf-ash (sparse-fur with abnormal skin and hair) mice during overnight-starvation and nitrogen loading. During starvation, spf-ash mice with about 6% and 2% of control levels of OTC activity in the liver and small intestine excreted a large amount of orotic acid in the urine. Transgenic spf-ash mice with about 10% and 30% of the control OTC activities in the liver and small intestine did not excrete more than the normal level of orotic acid. Accidental parasitization of transgenic spf-ash mice with ticks (Myocoptes musculinus) resulted in decrease of the OTC activities in the liver and small intestine to the levels in spf-ash mice, and increased excretion of orotic acid. During extermination of the ticks, the mice showed varied levels of OTC activity and orotic acid excretion. On nitrogen loading, transgenic spf-ash mice as well as spf-ash mice excreted larger amounts of orotic acid, while control mice showed no increase in its excretion. The levels of urinary orotic acid were inversely correlated to the logarithms of the OTC activities in the liver and small intestine, the correlation being significantly higher with intestinal OTC than with hepatic OTC activity. These results suggest that the level of OTC activity in the small intestine is important for production of orotic acid.
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PMID:Importance of ornithine transcarbamylase (OTC) deficiency in small intestine for urinary orotic acid excretion: analysis of OTC-deficient spf-ash mice with OTC transgene. 782 41

The sparse fur-abnormal skin and hair (SPF-ASH) mouse is a model for the human X-linked hereditary disease, ornithine transcarbamylase (OTC) deficiency. This condition is characterized by abnormal skin and delayed hair growth, hyperammonemia, orotic aciduria and low levels of serum citrulline and arginine. Murakami et al. [1] established a line of transgenic mice, by introducing the recombinant rat OTC (rOTC) gene into fertilized C57BL mouse eggs. We introduced the rOTC gene into SPF-ASH mice by mating SPF-ASH heterozygotes and transgenic mice, which carried this gene. The hemizygous SPF-ASH mice bearing the rOTC gene showed normal hair growth without sparse fur, normal urinary orotic acid excretion and normal serum citrulline and arginine levels. These mice showed OTC activities 2 and 6 times higher in the liver and small intestine, respectively, than the SPF-ASH mice but about 12% and 27% those of the controls [2].
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PMID:Normalization of hair growth in sparse fur-abnormal skin and hair (SPF-ASH) mice by introduction of the rat ornithine transcarbamylase (OTC) gene. 799 74


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