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Konrad Dabrowski - One of the best experts on this subject based on the ideXlab platform.
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EFFECT OF ASCORBIC ACID ENRICHMENT BY IMMERSION OF RAINBOW TROUT Oncorhynchus mykiss EGGS AND EMBRYOS
2015Co-Authors: Bahram Falahatkar, Murat Arslan, Jacques Rinchard, Konrad DabrowskiAbstract:Ascorbic acid is an essential micronutrient in the diet of teleost fish, including salmonids, which do not have Gulonolactone Oxidase activity (Moreau and Dabrowski, 2001). The ascorbic acid requirement for different teleost fish has been well documented (Dabrowski, 2001). This requirement may also vary in fish ontogeny, for instance larval metamorphosis or gonad maturation (Ciereszko and Dabrowski, 1995). Determination of factors that affect egg and larval quality remains difficult as good criteria are lacking (Kjorsvik e
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α-tocopherol downregulates Gulonolactone Oxidase activity in sturgeon
Free Radical Biology and Medicine, 2003Co-Authors: Régis Moreau, Konrad DabrowskiAbstract:Gulonolactone Oxidase (GLO) is the enzyme responsible for the last step of ascorbic acid biosynthesis. The aim of this study was to investigate the effect of dietary alpha-tocopherol and ascorbic acid on GLO activity in a lower vertebrate, the white sturgeon (Acipenser transmontanus). Both alpha-tocopherol and ascorbic acid modulated renal GLO activity. The increase of dietary levels of alpha-tocopherol and/or ascorbic acid significantly raised the liver concentrations of these two antioxidants and concomitantly lowered kidney's GLO activity. The results suggest that the enzyme of ascorbic acid synthetic pathway responded to the animal's antioxidant status and that its activity was downregulated by alpha-tocopherol. This is the first record of alpha-tocopherol being involved in the regulation of ascorbic acid synthesis. This new observation may provide a hypothesis for the evolutionary loss of GLO expression in teleost fishes.
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Biosynthesis of ascorbic acid by extant actinopterygians
Journal of Fish Biology, 2000Co-Authors: Régis Moreau, Konrad DabrowskiAbstract:Polypterus senegalus, the longnose gar Lepisosteus osseus and the bowfin Amia calva had Gulonolactone Oxidase activity in the kidney and thus can synthesize ascorbic acid de novo. The enzyme activity was associated with the microsomal fraction. The common carp Cyprinus carpio and the goldfish Carassius auratus had no Gulonolactone Oxidase activity. Antibodies directed against white sturgeon Gulonolactone Oxidase showed cross-reactivity with lake sturgeon, bowfin and longnose gar kidney enzymes, but not with enzymes from Polypterus, sea lamprey, and tadpole kidney or pig liver. Given cross-reactivity, Gulonolactone Oxidase relatedness matched actinopterygian phylogeny, and suggested homology of the character throughout fishes. Modern teleosts may have lost the ability to synthesize ascorbic acid since the late Triassic as a result of a single reversal in the founding population. Wild bowfin and longnose gar exhibited high ascorbate concentrations in liver and spleen when compared with the teleosts rainbow trout Oncorhynchus mykiss and common carp fed vitamin C-supplemented diets.
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Renal L-gulono-1,4-lactone Oxidase activity as affected by dietary ascorbic acid in lake sturgeon (Acipenser fulvescens)
Aquaculture, 1999Co-Authors: Régis Moreau, Konrad Dabrowski, Paul H. SatoAbstract:Abstract Sturgeon can synthesize l -ascorbic acid (vitamin C) as they possess in their kidney l -gulono-1,4-lactone Oxidase, the enzyme catalyzing the last step of AA biosynthesis. The effect of increasing dietary ascorbic acid on Gulonolactone Oxidase activity was studied in lake sturgeon. Two-year-old lake sturgeon (body weight 253±89 g) were fed in triplicate groups with casein-based semipurified diets supplemented with either 0, 50, 250 or 1250 mg ascorbic acid/kg in the form of ascorbyl-2-monophosphate Mg for 38 days at 19.8°C. At the end of the trial, there were no significant differences in growth rate and survival among groups. Tissue total ascorbic acid concentrations increased significantly with dietary ascorbic acid. Renal Gulonolactone Oxidase activity was inconsistently affected by dietary treatment. These results suggested that, in sturgeon kidney unlike in the livers of ascorbic acid-synthesizing mammals, dietary ascorbic acid did not exert a negative feedback control on Gulonolactone Oxidase activity and thus on ascorbic acid synthesized. Using in vitro kinetics data we estimated a theoretical biosynthetic rate of ascorbic acid of 17 μmol (or 3 mg) per kilogram body weight per day at 15°C in juvenile lake sturgeon.
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body pool and synthesis of ascorbic acid in adult sea lamprey petromyzon marinus an agnathan fish with Gulonolactone Oxidase activity
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Régis Moreau, Konrad DabrowskiAbstract:Although many vertebrates can synthesize ascorbic acid (vitamin C), it is still unclear from the evolutionary perspective when the ability to synthesize the vitamin first appeared in the animal kingdom and how frequently the trait has been lost. We report here ascorbic acid biosynthesis ability in sea lamprey (Petromyzon marinus) which represent the most ancient vertebrate lineage examined thus far for presence of Gulonolactone Oxidase, the enzyme catalyzing the terminal step in biosynthesis of vitamin C. This finding supports the view that the ancestors of living vertebrates were not scurvy prone and that the loss of Gulonolactone Oxidase activity subsequently occurred several times in vertebrate phylogeny. Adult sea lamprey allocate significant amounts of ascorbic acid to the gonads to guaranty high-quality gametes. Tissue stores of ascorbate were maintained by de novo synthesis (1.2–1.3 mg of ascorbic acid/300-g sea lamprey per day at 15°C) while sea lamprey fast during spawning migration. We estimate that the in vivo daily renewal rate of ascorbate is 4–5% of the whole-body ascorbate pool based on measurement of its biosynthesis and concentration in the whole animal.
Régis Moreau - One of the best experts on this subject based on the ideXlab platform.
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α-tocopherol downregulates Gulonolactone Oxidase activity in sturgeon
Free Radical Biology and Medicine, 2003Co-Authors: Régis Moreau, Konrad DabrowskiAbstract:Gulonolactone Oxidase (GLO) is the enzyme responsible for the last step of ascorbic acid biosynthesis. The aim of this study was to investigate the effect of dietary alpha-tocopherol and ascorbic acid on GLO activity in a lower vertebrate, the white sturgeon (Acipenser transmontanus). Both alpha-tocopherol and ascorbic acid modulated renal GLO activity. The increase of dietary levels of alpha-tocopherol and/or ascorbic acid significantly raised the liver concentrations of these two antioxidants and concomitantly lowered kidney's GLO activity. The results suggest that the enzyme of ascorbic acid synthetic pathway responded to the animal's antioxidant status and that its activity was downregulated by alpha-tocopherol. This is the first record of alpha-tocopherol being involved in the regulation of ascorbic acid synthesis. This new observation may provide a hypothesis for the evolutionary loss of GLO expression in teleost fishes.
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Biosynthesis of ascorbic acid by extant actinopterygians
Journal of Fish Biology, 2000Co-Authors: Régis Moreau, Konrad DabrowskiAbstract:Polypterus senegalus, the longnose gar Lepisosteus osseus and the bowfin Amia calva had Gulonolactone Oxidase activity in the kidney and thus can synthesize ascorbic acid de novo. The enzyme activity was associated with the microsomal fraction. The common carp Cyprinus carpio and the goldfish Carassius auratus had no Gulonolactone Oxidase activity. Antibodies directed against white sturgeon Gulonolactone Oxidase showed cross-reactivity with lake sturgeon, bowfin and longnose gar kidney enzymes, but not with enzymes from Polypterus, sea lamprey, and tadpole kidney or pig liver. Given cross-reactivity, Gulonolactone Oxidase relatedness matched actinopterygian phylogeny, and suggested homology of the character throughout fishes. Modern teleosts may have lost the ability to synthesize ascorbic acid since the late Triassic as a result of a single reversal in the founding population. Wild bowfin and longnose gar exhibited high ascorbate concentrations in liver and spleen when compared with the teleosts rainbow trout Oncorhynchus mykiss and common carp fed vitamin C-supplemented diets.
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Renal L-gulono-1,4-lactone Oxidase activity as affected by dietary ascorbic acid in lake sturgeon (Acipenser fulvescens)
Aquaculture, 1999Co-Authors: Régis Moreau, Konrad Dabrowski, Paul H. SatoAbstract:Abstract Sturgeon can synthesize l -ascorbic acid (vitamin C) as they possess in their kidney l -gulono-1,4-lactone Oxidase, the enzyme catalyzing the last step of AA biosynthesis. The effect of increasing dietary ascorbic acid on Gulonolactone Oxidase activity was studied in lake sturgeon. Two-year-old lake sturgeon (body weight 253±89 g) were fed in triplicate groups with casein-based semipurified diets supplemented with either 0, 50, 250 or 1250 mg ascorbic acid/kg in the form of ascorbyl-2-monophosphate Mg for 38 days at 19.8°C. At the end of the trial, there were no significant differences in growth rate and survival among groups. Tissue total ascorbic acid concentrations increased significantly with dietary ascorbic acid. Renal Gulonolactone Oxidase activity was inconsistently affected by dietary treatment. These results suggested that, in sturgeon kidney unlike in the livers of ascorbic acid-synthesizing mammals, dietary ascorbic acid did not exert a negative feedback control on Gulonolactone Oxidase activity and thus on ascorbic acid synthesized. Using in vitro kinetics data we estimated a theoretical biosynthetic rate of ascorbic acid of 17 μmol (or 3 mg) per kilogram body weight per day at 15°C in juvenile lake sturgeon.
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body pool and synthesis of ascorbic acid in adult sea lamprey petromyzon marinus an agnathan fish with Gulonolactone Oxidase activity
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Régis Moreau, Konrad DabrowskiAbstract:Although many vertebrates can synthesize ascorbic acid (vitamin C), it is still unclear from the evolutionary perspective when the ability to synthesize the vitamin first appeared in the animal kingdom and how frequently the trait has been lost. We report here ascorbic acid biosynthesis ability in sea lamprey (Petromyzon marinus) which represent the most ancient vertebrate lineage examined thus far for presence of Gulonolactone Oxidase, the enzyme catalyzing the terminal step in biosynthesis of vitamin C. This finding supports the view that the ancestors of living vertebrates were not scurvy prone and that the loss of Gulonolactone Oxidase activity subsequently occurred several times in vertebrate phylogeny. Adult sea lamprey allocate significant amounts of ascorbic acid to the gonads to guaranty high-quality gametes. Tissue stores of ascorbate were maintained by de novo synthesis (1.2–1.3 mg of ascorbic acid/300-g sea lamprey per day at 15°C) while sea lamprey fast during spawning migration. We estimate that the in vivo daily renewal rate of ascorbate is 4–5% of the whole-body ascorbate pool based on measurement of its biosynthesis and concentration in the whole animal.
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Ascorbic acid status as affected by dietary treatment in the Siberian sturgeon (Acipenser baeri Brandt): tissue concentration, mobilisation and L-Gulonolactone Oxidase activity
Fish Physiology and Biochemistry, 1996Co-Authors: Régis Moreau, Sadasivam J. Kaushik, Konrad DabrowskiAbstract:A study was conducted to evaluate tissue storage and mobilisation of L-ascorbic acid (AA) in the Siberian sturgeon ( Acipenser baeri ) fed three different experimental diets. The three treatments consisted of a diet devoid of vitamin C (diet A0) and two diets supplemented with equivalent of 300 mg AA kg^−1 in the form of either silicone-coated ascorbic acid (diet SC) or of ascorbyl-2-polyphosphate (diet AP). During the first phase (4 months) of the trial, six batches of 130 Siberian sturgeon (initial body weight: 25.5±0.5 g) each were fed one of the three diets in duplicate. During the second phase (3 months), fish from groups SC and AP were switched to diet A0 and those fed diet A0 during the first phase were switched to diet SC. Irrespective of the dietary treatment, growth rates were not significantly different from each other. At the end of phase I, in all tissues studied, total ascorbic acid (TAA) concentrations were higher in Siberian sturgeon fed diet AP than in the other two groups. During phase II, tissue ascorbate depletion was also higher in the AP group than in the other two groups. Transfer of the AA-free diet fed group onto a diet supplemented with 300 mg AA kg^−1 (diet SC) led to a slight increase in the TAA concentrations in all tissues. Blood plasma tyrosine concentrations were not significantly different between the three groups. Whole-body collagen levels were affected by dietary AA levels or forms at the end of phase I; the differences were not significant at the end of phase II. Muscle collagen levels were slightly affected. L-Gulonolactone Oxidase activity was found in the kidney of Siberian sturgeon, but not in the liver. The ascorbyl-2-polyphosphate appears to be either better utilised by Siberian sturgeon, like in many other teleosts, or more stable than the silicone-coated AA during food processing and storage. Presence of L-Gulonolactone Oxidase activity in Siberian sturgeon kidney combined with the absence of gross scorbutic signs in AA-free diet fed groups expressing very good growth rates suggested no need of dietary AA by A. baeri .
Herb E. Schellhorn - One of the best experts on this subject based on the ideXlab platform.
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Restoration of vitamin C synthesis in transgenic Gulo-/- mice by helper-dependent adenovirus-based expression of Gulonolactone Oxidase.
Human Gene Therapy, 2008Co-Authors: Chang-xin Shi, Karen L. Mossman, Jack Rosenfeld, Yong Chool Boo, Herb E. SchellhornAbstract:Inability to synthesize vitamin C, because of a deficiency in Gulonolactone Oxidase (GULO) expression, is a genetic deficiency shared by a small number of animals including humans. Although the most overt symptom of vitamin C deficiency, scurvy, can be readily corrected by modest consumption of vitamin C, there is increasing interest in the effect of high-level administration in treating human disease. Using a previously derived Gulo-expressing vector, which produces murine GULO under the control of the murine cytomegalovirus (mCMV) promoter, we constructed and validated a recombinant helper-dependent adenovirus (HDAd-mCMV-Gulo) that can be used to correct this genetic defect. A human liver cell line (Hep G2) infected with the HDAd-mCMV-Gulo vector expressed GULO in a time- and gene dose-dependent manner. These cells also produced ascorbic acid when exogenous Gulonolactone was supplemented in the medium. Likewise, Gulo(-/-) mice treated with HDAd-mCMV-Gulo at 2 x 10(11) VP expressed GULO in the liver and produced ascorbic acid. Serum ascorbic acid concentrations in Gulo(-/-) mice injected with GULO-expressing HDAd were elevated to levels comparable to those of wild-type mice (62 +/- 15 microM) after 4 days of infection and were maintained at significantly higher levels compared with those in untreated Gulo(-/-) mice for at least 23 days. A similar elevation was observed in urine and tissue ascorbic acid concentrations in vector-treated animals. In conclusion, we demonstrate here that gene therapeutic HDAd-mCMV-Gulo vectors can mediate the expression of GULO and endogenous production of ascorbic acid in human cells and in Gulo(-/-) transgenic mice. Taken together, these data show that a gene therapy approach can be successfully employed in the treatment and further study of vitamin C deficiency in scurvy-prone mammals.
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restoration of vitamin c synthesis in transgenic gulo mice by helper dependent adenovirus based expression of Gulonolactone Oxidase
Human Gene Therapy, 2008Co-Authors: Chang-xin Shi, Karen L. Mossman, Jack Rosenfeld, Yong Chool Boo, Herb E. SchellhornAbstract:Inability to synthesize vitamin C, because of a deficiency in Gulonolactone Oxidase (GULO) expression, is a genetic deficiency shared by a small number of animals including humans. Although the most overt symptom of vitamin C deficiency, scurvy, can be readily corrected by modest consumption of vitamin C, there is increasing interest in the effect of high-level administration in treating human disease. Using a previously derived Gulo-expressing vector, which produces murine GULO under the control of the murine cytomegalovirus (mCMV) promoter, we constructed and validated a recombinant helper-dependent adenovirus (HDAd-mCMV-Gulo) that can be used to correct this genetic defect. A human liver cell line (Hep G2) infected with the HDAd-mCMV-Gulo vector expressed GULO in a time- and gene dose-dependent manner. These cells also produced ascorbic acid when exogenous Gulonolactone was supplemented in the medium. Likewise, Gulo(-/-) mice treated with HDAd-mCMV-Gulo at 2 x 10(11) VP expressed GULO in the liver and produced ascorbic acid. Serum ascorbic acid concentrations in Gulo(-/-) mice injected with GULO-expressing HDAd were elevated to levels comparable to those of wild-type mice (62 +/- 15 microM) after 4 days of infection and were maintained at significantly higher levels compared with those in untreated Gulo(-/-) mice for at least 23 days. A similar elevation was observed in urine and tissue ascorbic acid concentrations in vector-treated animals. In conclusion, we demonstrate here that gene therapeutic HDAd-mCMV-Gulo vectors can mediate the expression of GULO and endogenous production of ascorbic acid in human cells and in Gulo(-/-) transgenic mice. Taken together, these data show that a gene therapy approach can be successfully employed in the treatment and further study of vitamin C deficiency in scurvy-prone mammals.
Jorge Vieira - One of the best experts on this subject based on the ideXlab platform.
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Multiple independent L-Gulonolactone Oxidase (GULO) gene losses and vitamin C synthesis reacquisition events in non-Deuterostomian animal species
BMC Evolutionary Biology, 2019Co-Authors: Sílvia F. Henriques, Pedro Duque, Hugo López-fernández, Florentino Fdez-riverola, Miguel Reboiro-jato, Noé Vázquez, Cristina P Vieira, Jorge VieiraAbstract:Background L-ascorbate (Vitamin C) is an important antioxidant and co-factor in eukaryotic cells, and in mammals it is indispensable for brain development and cognitive function. Vertebrates usually become L-ascorbate auxothrophs when the last enzyme of the synthetic pathway, an L-Gulonolactone Oxidase ( GULO ), is lost. Since Protostomes were until recently thought not to have a GULO gene, they were considered to be auxothrophs for Vitamin C. Results By performing phylogenetic analyses with tens of non-Bilateria and Protostomian genomes, it is shown, that a GULO gene is present in the non-Bilateria Placozoa, Myxozoa (here reported for the first time) and Anthozoa groups, and in Protostomians, in the Araneae family, the Gastropoda class, the Acari subclass (here reported for the first time), and the Priapulida, Annelida (here reported for the first time) and Brachiopoda phyla lineages. GULO is an old gene that predates the separation of Animals and Fungi, although it could be much older. We also show that within Protostomes, GULO has been lost multiple times in large taxonomic groups, namely the Pancrustacea, Nematoda, Platyhelminthes and Bivalvia groups, a pattern similar to that reported for Vertebrate species. Nevertheless, we show that Drosophila melanogaster seems to be capable of synthesizing L-ascorbate, likely through an alternative pathway, as recently reported for Caenorhabditis elegans . Conclusions Non-Bilaterian and Protostomians seem to be able to synthesize Vitamin C either through the conventional animal pathway or an alternative pathway, but in this animal group, not being able to synthesize L-ascorbate seems to be the exception rather than the rule.
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Multiple independent L-Gulonolactone Oxidase (GULO) gene losses and vitamin C synthesis reacquisition events in non-Deuterostomian animal species
BMC Evolutionary Biology, 2019Co-Authors: Sílvia Henriques, Pedro Duque, Hugo López-fernández, Florentino Fdez-riverola, Miguel Reboiro-jato, Noé Vázquez, Cristina P Vieira, Jorge VieiraAbstract:L-ascorbate (Vitamin C) is an important antioxidant and co-factor in eukaryotic cells, and in mammals it is indispensable for brain development and cognitive function. Vertebrates usually become L-ascorbate auxothrophs when the last enzyme of the synthetic pathway, an L-Gulonolactone Oxidase (GULO), is lost. Since Protostomes were until recently thought not to have a GULO gene, they were considered to be auxothrophs for Vitamin C. By performing phylogenetic analyses with tens of non-Bilateria and Protostomian genomes, it is shown, that a GULO gene is present in the non-Bilateria Placozoa, Myxozoa (here reported for the first time) and Anthozoa groups, and in Protostomians, in the Araneae family, the Gastropoda class, the Acari subclass (here reported for the first time), and the Priapulida, Annelida (here reported for the first time) and Brachiopoda phyla lineages. GULO is an old gene that predates the separation of Animals and Fungi, although it could be much older. We also show that within Protostomes, GULO has been lost multiple times in large taxonomic groups, namely the Pancrustacea, Nematoda, Platyhelminthes and Bivalvia groups, a pattern similar to that reported for Vertebrate species. Nevertheless, we show that Drosophila melanogaster seems to be capable of synthesizing L-ascorbate, likely through an alternative pathway, as recently reported for Caenorhabditis elegans. Non-Bilaterian and Protostomians seem to be able to synthesize Vitamin C either through the conventional animal pathway or an alternative pathway, but in this animal group, not being able to synthesize L-ascorbate seems to be the exception rather than the rule.
Chang-xin Shi - One of the best experts on this subject based on the ideXlab platform.
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Restoration of vitamin C synthesis in transgenic Gulo-/- mice by helper-dependent adenovirus-based expression of Gulonolactone Oxidase.
Human Gene Therapy, 2008Co-Authors: Chang-xin Shi, Karen L. Mossman, Jack Rosenfeld, Yong Chool Boo, Herb E. SchellhornAbstract:Inability to synthesize vitamin C, because of a deficiency in Gulonolactone Oxidase (GULO) expression, is a genetic deficiency shared by a small number of animals including humans. Although the most overt symptom of vitamin C deficiency, scurvy, can be readily corrected by modest consumption of vitamin C, there is increasing interest in the effect of high-level administration in treating human disease. Using a previously derived Gulo-expressing vector, which produces murine GULO under the control of the murine cytomegalovirus (mCMV) promoter, we constructed and validated a recombinant helper-dependent adenovirus (HDAd-mCMV-Gulo) that can be used to correct this genetic defect. A human liver cell line (Hep G2) infected with the HDAd-mCMV-Gulo vector expressed GULO in a time- and gene dose-dependent manner. These cells also produced ascorbic acid when exogenous Gulonolactone was supplemented in the medium. Likewise, Gulo(-/-) mice treated with HDAd-mCMV-Gulo at 2 x 10(11) VP expressed GULO in the liver and produced ascorbic acid. Serum ascorbic acid concentrations in Gulo(-/-) mice injected with GULO-expressing HDAd were elevated to levels comparable to those of wild-type mice (62 +/- 15 microM) after 4 days of infection and were maintained at significantly higher levels compared with those in untreated Gulo(-/-) mice for at least 23 days. A similar elevation was observed in urine and tissue ascorbic acid concentrations in vector-treated animals. In conclusion, we demonstrate here that gene therapeutic HDAd-mCMV-Gulo vectors can mediate the expression of GULO and endogenous production of ascorbic acid in human cells and in Gulo(-/-) transgenic mice. Taken together, these data show that a gene therapy approach can be successfully employed in the treatment and further study of vitamin C deficiency in scurvy-prone mammals.
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restoration of vitamin c synthesis in transgenic gulo mice by helper dependent adenovirus based expression of Gulonolactone Oxidase
Human Gene Therapy, 2008Co-Authors: Chang-xin Shi, Karen L. Mossman, Jack Rosenfeld, Yong Chool Boo, Herb E. SchellhornAbstract:Inability to synthesize vitamin C, because of a deficiency in Gulonolactone Oxidase (GULO) expression, is a genetic deficiency shared by a small number of animals including humans. Although the most overt symptom of vitamin C deficiency, scurvy, can be readily corrected by modest consumption of vitamin C, there is increasing interest in the effect of high-level administration in treating human disease. Using a previously derived Gulo-expressing vector, which produces murine GULO under the control of the murine cytomegalovirus (mCMV) promoter, we constructed and validated a recombinant helper-dependent adenovirus (HDAd-mCMV-Gulo) that can be used to correct this genetic defect. A human liver cell line (Hep G2) infected with the HDAd-mCMV-Gulo vector expressed GULO in a time- and gene dose-dependent manner. These cells also produced ascorbic acid when exogenous Gulonolactone was supplemented in the medium. Likewise, Gulo(-/-) mice treated with HDAd-mCMV-Gulo at 2 x 10(11) VP expressed GULO in the liver and produced ascorbic acid. Serum ascorbic acid concentrations in Gulo(-/-) mice injected with GULO-expressing HDAd were elevated to levels comparable to those of wild-type mice (62 +/- 15 microM) after 4 days of infection and were maintained at significantly higher levels compared with those in untreated Gulo(-/-) mice for at least 23 days. A similar elevation was observed in urine and tissue ascorbic acid concentrations in vector-treated animals. In conclusion, we demonstrate here that gene therapeutic HDAd-mCMV-Gulo vectors can mediate the expression of GULO and endogenous production of ascorbic acid in human cells and in Gulo(-/-) transgenic mice. Taken together, these data show that a gene therapy approach can be successfully employed in the treatment and further study of vitamin C deficiency in scurvy-prone mammals.