The Experts below are selected from a list of 225 Experts worldwide ranked by ideXlab platform
Weikuan Gu - One of the best experts on this subject based on the ideXlab platform.
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Genome Wide Analysis of Sex Difference in Gene Expression Profiles of Bone Formations Using sfx Mice and BXD RI Strains
The Scientific World Journal, 2014Co-Authors: Yue Huang, Weikuan Gu, Lishi Wang, Lu Lu, Yan JiaoAbstract:The objective of this study is to identify sex differentially expressed genes in bone using a mouse model of spontaneous fracture, sfx, which lacks the gene for L-Gulonolactone Oxidase (Gulo), a key enzyme in the ascorbic acid (AA) synthesis pathway. We first identified the genes that are differentially expressed in the femur between female and male in sfx mice. We then analyzed the potential gene network among those differentially expressed genes with whole genome expression profiles generated using spleens of female and male mice of a total of 67 BXD (C57BL/6J X DBA/2J) recombinant inbred (RI) and other strains. Our result indicated that there was a sex difference in the whole genome profiles in sfx mice as measured by the proportion of up- and downregulated genes. Several genes in the pathway of bone development are differentially expressed between the male and female of sfx mice. Comparison of gene network of up- and downregulated bone relevant genes also suggests a sex difference.
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Genome-Wide Gene Expression Profiles in Antioxidant Pathways and Their Potential Sex Differences and Connections to Vitamin C in Mice
International Journal of Molecular Sciences, 2013Co-Authors: Yan Jiao, Yue Huang, Lishi Wang, Lu Lu, Hong Chen, Robert W. Williams, Yongjun Wang, Weikuan GuAbstract:Vitamin C (VC) is well known as an antioxidant in humans, primates and guinea pigs. Studies have suggested gender differences in VC requirements in humans, and gender differences in oxidant injury vulnerability in early life may represent a biological mechanism contributing to gender disparity in later life. Using spontaneous bone fracture (sfx) mice, which lack the gene for L-Gulonolactone Oxidase (Gulo), we studied the potential sex difference in expression profiles of oxidative genes at the whole-genome level. Then, we analyzed data of gene expressions in a mouse population of recombinant inbred (RI) strains originally derived by crossing C57BL/6J (B6) and DBA/2J (D2) mice. Our data indicated that there were sex differences in the regulation of pre- and pro-oxidative genes in sfx mice. The associations of expression levels among Gulo, its partner genes and oxidative genes in the BXD (B6 × D2) RI strains showed a sex difference. Transcriptome mapping suggests that Gulo was regulated differently between female and male mice in BXD RI strains. Our study indicates the importance of investigating sex differences in Gulo and its oxidative function by using available mouse models.
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Evaluation of potential role of vitamin C in differential skeletal development between female and male mice using a mouse model.
BMC Bioinformatics, 2012Co-Authors: Yan Jiao, Yonghui Ma, Weikuan GuAbstract:Background In humans, gender difference has been suggested by previous studies. Sex difference in vitamin C requirements have also been reported from animal models. Mouse spontaneous fracture model (sfx) lacks L-Gulonolactone Oxidase (LGO), an essential gene for the synthesis of ascorbic acid (Vitamin C). We have been using sfx model for the past eight years and we are the first group to identify the LGO mutation in this mouse model.
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Evaluation of gene expression in muscle in mouse model lacking of vitamin C synthesis
BMC Bioinformatics, 2012Co-Authors: Yonghui Ma, Yan Jiao, Fusheng Zhao, Weikuan GuAbstract:Background Human species and guinea pigs have to obtain vitamin C (VC) from food because they are unable to synthesize ascorbic acid due to the absence of the gene that encodes L-Gulonolactone Oxidase (Gulo). The spontaneous bone fracture (sfx) mouse is a mouse model which is deficient in the synthesis of VC because of the deletion in Gulo gene. Because muscle forces are a strong determinant of bone structure, particularly during the process of growth and development, we examined the gene expression of muscle in sfx mice.
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Differential gene expression between wild-type and Gulo-deficient mice supplied with vitamin C.
Genetics and Molecular Biology, 2011Co-Authors: Yan Jiao, Lu Lu, Yongjun Wang, Jifei Zhang, John M. Stuart, Griffin Gibson, Robert Willaims, Weikuan GuAbstract:The aim of this study was to test the hypothesis that hepatic vitamin C (VC) levels in VC deficient mice rescued with high doses of VC supplements still do not reach the optimal levels present in wild-type mice. For this, we used a mouse scurvy model (sfx) in which the L-Gulonolactone Oxidase gene (Gulo) is deleted. Six age- (6 weeks old) and gender- (female) matched wild-type (WT) and sfx mice (rescued by administering 500 mg of VC/L) were used as the control (WT) and treatment (MT) groups (n = 3 for each group), respectively. Total hepatic RNA was used in triplicate microarray assays for each group. EDGE software was used to identify differentially expressed genes and transcriptomic analysis was used to assess the potential genetic regulation of Gulo gene expression. Hepatic VC concentrations in MT mice were significantly lower than in WT mice, even though there were no morphological differences between the two groups. In MT mice, 269 differentially expressed transcripts were detected (> twice the difference between MT and WT mice), including 107 up-regulated and 162 down-regulated genes. These differentially expressed genes included stress-related and exclusively/predominantly hepatocyte genes. Transcriptomic analysis identified a major locus on chromosome 18 that regulates Gulo expression. Since three relevant oxidative genes are located within the critical region of this locus we suspect that they are involved in the down-regulation of oxidative activity in sfx mice.
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, Noé Vázquez, Florentino Fdez-riverola, Miguel Reboiro-jato, 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, Noé Vázquez, Florentino Fdez-riverola, Miguel Reboiro-jato, 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.
Yan Jiao - One of the best experts on this subject based on the ideXlab platform.
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Genome Wide Analysis of Sex Difference in Gene Expression Profiles of Bone Formations Using sfx Mice and BXD RI Strains
The Scientific World Journal, 2014Co-Authors: Yue Huang, Weikuan Gu, Lishi Wang, Lu Lu, Yan JiaoAbstract:The objective of this study is to identify sex differentially expressed genes in bone using a mouse model of spontaneous fracture, sfx, which lacks the gene for L-Gulonolactone Oxidase (Gulo), a key enzyme in the ascorbic acid (AA) synthesis pathway. We first identified the genes that are differentially expressed in the femur between female and male in sfx mice. We then analyzed the potential gene network among those differentially expressed genes with whole genome expression profiles generated using spleens of female and male mice of a total of 67 BXD (C57BL/6J X DBA/2J) recombinant inbred (RI) and other strains. Our result indicated that there was a sex difference in the whole genome profiles in sfx mice as measured by the proportion of up- and downregulated genes. Several genes in the pathway of bone development are differentially expressed between the male and female of sfx mice. Comparison of gene network of up- and downregulated bone relevant genes also suggests a sex difference.
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Genome-Wide Gene Expression Profiles in Antioxidant Pathways and Their Potential Sex Differences and Connections to Vitamin C in Mice
International Journal of Molecular Sciences, 2013Co-Authors: Yan Jiao, Yue Huang, Lishi Wang, Lu Lu, Hong Chen, Robert W. Williams, Yongjun Wang, Weikuan GuAbstract:Vitamin C (VC) is well known as an antioxidant in humans, primates and guinea pigs. Studies have suggested gender differences in VC requirements in humans, and gender differences in oxidant injury vulnerability in early life may represent a biological mechanism contributing to gender disparity in later life. Using spontaneous bone fracture (sfx) mice, which lack the gene for L-Gulonolactone Oxidase (Gulo), we studied the potential sex difference in expression profiles of oxidative genes at the whole-genome level. Then, we analyzed data of gene expressions in a mouse population of recombinant inbred (RI) strains originally derived by crossing C57BL/6J (B6) and DBA/2J (D2) mice. Our data indicated that there were sex differences in the regulation of pre- and pro-oxidative genes in sfx mice. The associations of expression levels among Gulo, its partner genes and oxidative genes in the BXD (B6 × D2) RI strains showed a sex difference. Transcriptome mapping suggests that Gulo was regulated differently between female and male mice in BXD RI strains. Our study indicates the importance of investigating sex differences in Gulo and its oxidative function by using available mouse models.
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Evaluation of potential role of vitamin C in differential skeletal development between female and male mice using a mouse model.
BMC Bioinformatics, 2012Co-Authors: Yan Jiao, Yonghui Ma, Weikuan GuAbstract:Background In humans, gender difference has been suggested by previous studies. Sex difference in vitamin C requirements have also been reported from animal models. Mouse spontaneous fracture model (sfx) lacks L-Gulonolactone Oxidase (LGO), an essential gene for the synthesis of ascorbic acid (Vitamin C). We have been using sfx model for the past eight years and we are the first group to identify the LGO mutation in this mouse model.
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Evaluation of gene expression in muscle in mouse model lacking of vitamin C synthesis
BMC Bioinformatics, 2012Co-Authors: Yonghui Ma, Yan Jiao, Fusheng Zhao, Weikuan GuAbstract:Background Human species and guinea pigs have to obtain vitamin C (VC) from food because they are unable to synthesize ascorbic acid due to the absence of the gene that encodes L-Gulonolactone Oxidase (Gulo). The spontaneous bone fracture (sfx) mouse is a mouse model which is deficient in the synthesis of VC because of the deletion in Gulo gene. Because muscle forces are a strong determinant of bone structure, particularly during the process of growth and development, we examined the gene expression of muscle in sfx mice.
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Differential gene expression between wild-type and Gulo-deficient mice supplied with vitamin C.
Genetics and Molecular Biology, 2011Co-Authors: Yan Jiao, Lu Lu, Yongjun Wang, Jifei Zhang, John M. Stuart, Griffin Gibson, Robert Willaims, Weikuan GuAbstract:The aim of this study was to test the hypothesis that hepatic vitamin C (VC) levels in VC deficient mice rescued with high doses of VC supplements still do not reach the optimal levels present in wild-type mice. For this, we used a mouse scurvy model (sfx) in which the L-Gulonolactone Oxidase gene (Gulo) is deleted. Six age- (6 weeks old) and gender- (female) matched wild-type (WT) and sfx mice (rescued by administering 500 mg of VC/L) were used as the control (WT) and treatment (MT) groups (n = 3 for each group), respectively. Total hepatic RNA was used in triplicate microarray assays for each group. EDGE software was used to identify differentially expressed genes and transcriptomic analysis was used to assess the potential genetic regulation of Gulo gene expression. Hepatic VC concentrations in MT mice were significantly lower than in WT mice, even though there were no morphological differences between the two groups. In MT mice, 269 differentially expressed transcripts were detected (> twice the difference between MT and WT mice), including 107 up-regulated and 162 down-regulated genes. These differentially expressed genes included stress-related and exclusively/predominantly hepatocyte genes. Transcriptomic analysis identified a major locus on chromosome 18 that regulates Gulo expression. Since three relevant oxidative genes are located within the critical region of this locus we suspect that they are involved in the down-regulation of oxidative activity in sfx mice.
Stefan Neuenschwander - One of the best experts on this subject based on the ideXlab platform.
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Intragenic deletion in the gene encoding L-Gulonolactone Oxidase causes vitamin C deficiency in pigs
Mammalian Genome, 2004Co-Authors: Lara Hasan, Peter Vögeli, Peter Stoll, Špela Špilar Gerald Kramerstranzinger, Stefan NeuenschwanderAbstract:The absence of L -ascorbic acid (L-AA, or AA) synthesis in scurvy-prone organisms, including humans, other primates, guinea pigs, and flying mammals, was traced to the lack of L -gulonolactone Oxidase (GULO) activity. GULO is a microsomal enzyme that catalyzes the terminal step in the biosynthesis of L-AA. Clinical cases of scurvy were described in a family of Danish pigs. This trait is controlled by a single autosomal recessive allele designated od (osteogenic disorder). Here we demonstrate that the absence of GULO activity and the associated vitamin C deficiency in od/od pigs is due to the occurrence of a 4.2-kbp deletion in the GULO gene. This deletion includes 77 bp of exon VIII, 398 bp of intron 7 and 3.7 kbp of intron 8, which leads to a frame shift. The mutant protein is truncated to 356 amino acids, but only the first 236 amino acids are identical to the wild-type GULO protein. In addition, the od allele seems to be less expressed in deficient and heterozygous pigs compared with the normal allele in heterozygous and wild-type animals as determined by ribonuclease protection assay. We also developed a DNA-based test for the diagnosis of the deficient allele. However, we failed to identify the mutated allele in other pig populations.
D. V. Maurice - One of the best experts on this subject based on the ideXlab platform.
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Sexual difference in ascorbic acid synthesis, tissue ascorbic acid and plasma total antioxidant capacity in mature chickens
British Poultry Science, 2020Co-Authors: D. V. Maurice, S. F. LightseyAbstract:1. An experiment was conducted with commercial White Leghorn type chickens to determine the effect of gender on tissue ascorbic acid concentration, antioxidant capacity and ascorbic acid synthesis. 2. Birds reared and maintained on litter were given a standard layer diet, without supplemental ascorbic acid, from 18 weeks of age. Tissue ascorbic acid concentration, plasma total antioxidant capacity and renal L-Gulonolactone Oxidase activity were measured at 30 weeks of age. 3. Females and males differed in ascorbic acid synthesis, as measured by renal L-Gulonolactone Oxidase activity, and tissue ascorbic acid concentration. 4. Plasma total antioxidant capacity and adrenal, gonadal, plasma and pituitary ascorbic acid concentrations were significantly higher in males, whereas ascorbic acid synthesis and splenic and thymic ascorbic acid concentrations were significantly higher in females. 5. L-Gulonolactone Oxidase activity was not detected in the comb of cockerels.
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L-Gulonolactone Oxidase Activity, Tissue Ascorbic Acid and Total Antioxidant Capacity in Vitamin A-Deficient Chickens, Gallus gallus
Journal of Poultry Science, 2009Co-Authors: D. V. Maurice, S. F. Lightsey, Joe E. Toler, Alaeldien Abudabos, Heidi LindlerAbstract:Experiments were conducted to determine the effect of vitamin A deficiency in chicks on tissue ascorbic acid, plasma oxidant status and antioxidant capacity, and renal L-Gulonolactone Oxidase activity (GULO) in broiler chickens. Chicks were reared in battery cages and fed a practical diet with vitamin A (control) or the same diet without supplemental vitamin A from day-old to 23 or 30 days of age. The treatments were arranged in a randomized complete block design with 6-8 replications. At termination body weight, feed intake, and tissue weights were recorded and tissues analysed for ascorbic acid, GULO activity, antioxidant activty, and oxidant status. Growth, feed intake, relative weights of bursa of Fabricius, liver, spleen and testis were significantly reduced in vitamin A-deficient chicks. Vitamin A deficiency depressed renal GULO activity by 20% (P
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Effect of chronic oxidative/corticosterone‐induced stress on ascorbic acid metabolism and total antioxidant capacity in chickens (Gallus gallus domesticus)
Journal of Animal Physiology and Animal Nutrition, 2007Co-Authors: D. V. Maurice, S. F. Lightsey, Joe E. Toler, S. CantyAbstract:Summary The consequences of chronic corticosterone-induced stress (CCIS) on ascorbic acid (AsA) metabolism in chickens, an animal that syntheses the vitamin, are not known. This study was conducted to determine whether CCIS alters AsA synthesis, as measured by L-Gulonolactone Oxidase (GLO) activity, tissue AsA, lipid peroxides and tissue total antioxidant capacity (TAC). Stress was induced by dietary administration of corticosterone from 2 to 4 weeks of age and measurements were made at 0, 7 and 14 days post-treatment. Ascorbic acid synthesis was not influenced by CCIS but hepatic, cardiac, renal, bursal and duodenal AsA concentrations were significantly decreased and plasma TAC and uric acid concentrations were significantly elevated. Stress caused significant hepatomegaly and hepatic lipidosis but hepatic peroxides were not elevated despite the slight decrease in hepatic TAC. Tissue TAC varied in different organs. It was markedly elevated in the kidney, reduced by 49% in the spleen, and changes were not detected in the heart and duodenum even though AsA concentration was significantly decreased in all tissues. We conclude that CCIS caused a significant reduction in tissue AsA concentration but did not inhibit GLO activity. The change in AsA concentration was associated with increase, decrease or no change in TAC in tissues examined. The findings suggest that CCIS may alter AsA recycling, influx or turnover in different tissues of chickens.
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Ascorbic acid biosynthesis in hens producing strong and weak eggshells
British Poultry Science, 2004Co-Authors: D. V. Maurice, S. F. Lightsey, Joe E. TolerAbstract:1. An experiment was conducted with two strains of layers to ascertain whether the reduction in eggshell strength occurring at the end of the production cycle is the result of reduced ascorbic acid biosynthesis. 2. Hens producing strong and weak eggshells were identified within each strain and egg production, egg weight, per cent shell, shell surface density, plasma, adrenal and hepatic ascorbic acid and renal L-Gulonolactone Oxidase activity were measured. 3. The strains differed in ascorbic acid synthesis, as measured by L-Gulonolactone Oxidase activity, and tissue ascorbic acid concentration. 4. Comparison of results from birds producing eggs of similar weight but markedly different in shell strength detected neither a shell strength group × strain interaction nor an effect of shell strength group on plasma and hepatic ascorbic acid and activity of L-Gulonolactone Oxidase. 5. The results did not support the hypothesis that tissue ascorbate and ascorbic acid biosynthesis are reduced in old hens producin...
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Factors affecting ascorbic acid biosynthesis in chickens: III. Effect of dietary fluoride on L-Gulonolactone Oxidase activity and tissue ascorbic acid (AsA) concentration
Journal of Animal Physiology and Animal Nutrition, 2002Co-Authors: D. V. Maurice, S. F. Lightsey, Alaeldein M. Abudabos, Joe E. TolerAbstract:Summary The inconsistent beneficial responses to dietary ascorbic acid (AsA) may be due to dietary factors that alter biosynthesis or tissue turnover of AsA. It has been suggested on the basis of altered tissue AsA that dietary fluoride is a determinant of biosynthesis in chickens. Fluoride may enter the food chain of poultry via industrial contamination, feed ingredients and drinking water. The goal of this study was to ascertain whether dietary fluoride at 300 mg/kg influences L-Gulonolactone Oxidase (GLO) activity in commercial meat-type chickens. The experimental diet was fed from day-old to 3 weeks and responses measured. Growth and feed conversion were not affected by fluoride in the diet. Dietary fluoride neither inhibited nor enhanced GLO activity nor did it increase or decrease AsA concentration in plasma, liver, kidney, adrenal gland and muscle (pectoralis major). Tissue AsA concentration in ascending order was adrenal > liver > kidney > pectoralis major > plasma. The results are consistent with that reported for the rat and calculations based on the results eliminate fluorine contamination for the inconsistent responses of immature chickens to dietary AsA.
