Loss of Nnt Increases Expression of Oxidative Phosphorylation Complexes in C57BL/6J Hearts
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Volume
22
Publisher
DOI
10.3390/ijms22116101
Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Issue
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Nicotinamide nucleotide transhydrogenase (NNT) is a proton pump in the inner mitochondrial membrane that generates reducing equivalents in the form of NAPDH, which can be
used for anabolic pathways or to remove reactive oxygen species (ROS). A number of studies have
linked NNT dysfunction to cardiomyopathies and increased risk of atherosclerosis; however, biallelic
mutations in humans commonly cause a phenotype of adrenal insufficiency, with rare occurrences
of cardiac dysfunction and testicular tumours. Here, we compare the transcriptomes of the hearts,
adrenals and testes from three mouse models: the C57BL/6N, which expresses NNT; the C57BL/6J,
which lacks NNT; and a third mouse, expressing the wild-type NNT sequence on the C57BL/6J
background. We saw enrichment of oxidative phosphorylation genes in the C57BL/B6J in the heart
and adrenal, possibly indicative of an evolved response in this substrain to loss of Nnt. However,
differential gene expression was mainly driven by mouse background with some changes seen
in all three tissues, perhaps reflecting underlying genetic differences between the C57BL/B6J and
-6N substrains.
Authors
Williams, JL; Hall, CL; Meimaridou, E; Metherell, LACollections
- Centre for Endocrinology [560]