Differential gene expression between wild-type and Gulo-deficient mice supplied with vitamin C.

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.

Differential gene expression between wild-type and Gulo-deficient mice supplied with vitamin C

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.

Evaluation of gene expression profiling in a mouse model of L-gulonolactone oxidase gene deficiency

Humans and guinea pigs are species which are unable to synthesize ascorbic acid (vitamin C) because, unlike rodents, they lack the enzyme L-gulonolactone oxidase (Gulo). Although the phenotype of lacking vitamin C in humans, named scurvy, has long been well known, information on the impact of lacking Gulo on the gene expression profiles of different tissues is still missing. This knowledge could improve our understanding of molecular pathways in which Gulo may be involved. Recently, we discovered a deletion that includes all 12 exons in the gene for Gulo in the sfx mouse, characterized by spontaneous bone fractures. We report here the initial analysis of the impact of the Gulo gene deletion on the murine gene expression profiles in the liver, femur and kidney.

Evaluation of gene expression profiling in a mouse model of L-gulonolactone oxidase gene deficiency.

Humans and guinea pigs are species which are unable to synthesize ascorbic acid (vitamin C) because, unlike rodents, they lack the enzyme L-gulonolactone oxidase (Gulo). Although the phenotype of lacking vitamin C in humans, named scurvy, has long been well known, information on the impact of lacking Gulo on the gene expression profiles of different tissues is still missing. This knowledge could improve our understanding of molecular pathways in which Gulo may be involved. Recently, we discovered a deletion that includes all 12 exons in the gene for Gulo in the sfx mouse, characterized by spontaneous bone fractures. We report here the initial analysis of the impact of the Gulo gene deletion on the murine gene expression profiles in the liver, femur and kidney.