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Transcription profiling of mouse Hexose-6-phosphate dehydrogenase knockout muscle at 4 weeks


ABSTRACT: Hexose-6-phosphate dehydrogenase (H6PD)is the initial component of a pentose phosphate pathway inside the endoplasmic reticulum (ER) that generates NADPH for ER enzymes. In liver, H6PD is required for the 11-oxoreductase activity of 11ss-hydroxysteroid dehydrogenase type 1 (11ss-HSD1), which converts inactive 11-oxo glucocorticoids to their active 11-hydroxyl counterparts; consequently, H6PD null mice are relatively insensitive to glucocorticoids, exhibiting fasting hypoglycemia, increased insulin sensitivity despite elevated circulating levels of corticosterone, and increased basal and insulin-stimulated glucose uptake in muscles normally enriched in Type II (fast) fibers which have increased glycogen content. They also display a progressive vacuolar myopathy evident after 4 weeks of age. We carried out microarray analysis on TA and soleus muscles from 4 week old WT and KO mice to determine an expression profile predicting myopathy. Experiment Overall Design: 4 week old mice are weaned and do not display overt histological evidence of myopathy. Soleus and tibialis anterior are used as comparison groups as they have distinct fibre type content and differing metabolic properties. 3 biological replicates are used for each genotpye and sample type.

ORGANISM(S): Mus musculus

SUBMITTER: Gareth Lavery 

PROVIDER: E-GEOD-10347 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Deletion of hexose-6-phosphate dehydrogenase activates the unfolded protein response pathway and induces skeletal myopathy.

Lavery Gareth G GG   Walker Elizabeth A EA   Turan Nil N   Rogoff Daniela D   Ryder Jeffery W JW   Shelton John M JM   Richardson James A JA   Falciani Francesco F   White Perrin C PC   Stewart Paul M PM   Parker Keith L KL   McMillan Daniel R DR  

The Journal of biological chemistry 20080125 13


Hexose-6-phosphate dehydrogenase (H6PD) is the initial component of a pentose phosphate pathway inside the endoplasmic reticulum (ER) that generates NADPH for ER enzymes. In liver H6PD is required for the 11-oxoreductase activity of 11beta-hydroxysteroid dehydrogenase type 1, which converts inactive 11-oxo-glucocorticoids to their active 11-hydroxyl counterparts; consequently, H6PD null mice are relatively insensitive to glucocorticoids, exhibiting fasting hypoglycemia, increased insulin sensiti  ...[more]

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