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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 15, 2012 |
| Title |
Ascorbic acid depletion and scorbutic extracellular matrix in mice deficient in endoplasmic reticulum thiol oxidases |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Endoplasmic reticulum (ER) thiol oxidases initiate a disulfide relay to oxidatively-fold secreted proteins. We found that combined loss-of-function mutations in genes encoding the ER thiol oxidases ERO1alpha, ERO1beta and PRDX4, compromised the extracellular matrix in mice and interfered with the intracellular maturation of procollagen. These severe abnormalities were associated with an unexpectedly-modest delay in disulfide bond formation in secreted proteins but a profound, five-fold lower procollagen 4 hydroxyproline content and enhanced cysteinyl sulfenic acid modification of ER proteins. Tissue ascorbic acid content was lower in mutant mice and ascorbic acid supplementation improved procollagen maturation and lowered sulfenic acid content, in vivo. In vitro, the presence of a sulfenic acid donor accelerated the oxidative inactivation of ascorbate by an H2O2 generating system. Compromised ER disulfide relay thus exposes protein thiols to competing oxidation to sulfenic acid, resulting in depletion of ascorbic acid, impaired procollagen proline 4-hydroxylation and a non-canonical form of scurvy.
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| Overall design |
double and triple mutants and wild type
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| Contributor(s) |
Zito E, Ron D |
| Citation(s) |
22981861 |
| Submission date |
Jul 19, 2012 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Brian Yee Hong Lam |
| E-mail(s) |
yhbl2@cam.ac.uk
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| Organization name |
University of Cambridge
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| Department |
Metabolic Research Laboratories
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| Street address |
Box 289 Addenbookes Hospital, Hills Road
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0QQ |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (9)
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| GSM970185 |
ERO1alpha and beta double mutant 1 |
| GSM970186 |
ERO1alpha and beta double mutant 2 |
| GSM970187 |
ERO1alpha and beta double mutant 3 |
| GSM970188 |
PRDX4 KO, ERO1alpha and beta double mutant 1 |
| GSM970189 |
PRDX4 KO, ERO1alpha and beta double mutant 2 |
| GSM970190 |
PRDX4 KO, ERO1alpha and beta double mutant 3 |
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| Relations |
| BioProject |
PRJNA170982 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE39492_RAW.tar |
42.6 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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