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Fig. 7. The muscular hypoxia-response is HIF-1 dependent. Spontaneously active HIF-1 heterozygous-deficient mice (HIF-1–/+) and wild-type mice (WT) were subjected to 24 h of normoxia (21% O₂) or hypoxia (10.5% O₂, N=6/group). M. solei were harvested from the four experimental groups and analyzed with custom-designed microarrays for expression of 222 muscle-relevant transcripts (Fluck et al., 2005a; Dapp et al., 2004). The hypoxia-to-normoxia signal ratio of 142 detected transcripts was assessed by descriptive cluster analysis (A) and probability testing (B,C) to identify genotype-dependent differences in the hypoxia response (Däpp et al., 2006). (A) Hierarchical cluster analysis visualizing the global pattern of hypoxia-induced expression changes for the different experiments. The correlations (r) of the transcript response in hypoxia are reflected by the line length in the dendrogram. Alterations of expression levels for each transcript and experiment are given in color coding (up, red; down, blue). The clustering was recalculated as described (Fluck et al., 2005b) for centered correlations from the data of (Däpp et al., 2006) using log-transformed and mean-centered data. Note: the hypoxia expression patterns group according to the respective genotype. Distinct clusters of HIF-1-dependent transcripts, which demonstrate co-regulated level changes upon hypoxia and whose response was `inverted' in HIF-1 deficient muscle, are boxed. (B,C) Mean and standard error of significant transcript level differences for factors involved in the successive steps of glycolysis (B) and fatty acid metabolism (C). Gene expression alterations in HIF-1–/+ mice are shown in pink. Note: the muscular transcript response of glycolytic and oxidative pathways in hypoxia is reversed in HIF-1-deficient mice.

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