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Broad AOX expression in a genetically tractable mouse model does not disturb normal physiology
- Source :
- Disease Models & Mechanisms, Vol 10, Iss 2, Pp 163-171 (2017), Disease models & mechanisms, 10(2): 163-171, Disease Models & Mechanisms, Dis. Model. Mech. 10, 163-171 (2017)
- Publication Year :
- 2017
-
Abstract
- Plants and many lower organisms, but not mammals, express alternative oxidases (AOXs) that branch the mitochondrial respiratory chain, transferring electrons directly from ubiquinol to oxygen without proton pumping. Thus, they maintain electron flow under conditions when the classical respiratory chain is impaired, limiting excess production of oxygen radicals and supporting redox and metabolic homeostasis. AOX from Ciona intestinalis has been used to study and mitigate mitochondrial impairments in mammalian cell lines, Drosophila disease models and, most recently, in the mouse, where multiple lentivector-AOX transgenes conferred substantial expression in specific tissues. Here, we describe a genetically tractable mouse model in which Ciona AOX has been targeted to the Rosa26 locus for ubiquitous expression. The AOXRosa26 mouse exhibited only subtle phenotypic effects on respiratory complex formation, oxygen consumption or the global metabolome, and showed an essentially normal physiology. AOX conferred robust resistance to inhibitors of the respiratory chain in organello; moreover, animals exposed to a systemically applied LD50 dose of cyanide did not succumb. The AOXRosa26 mouse is a useful tool to investigate respiratory control mechanisms and to decipher mitochondrial disease aetiology in vivo.<br />Summary: Previous limitations are overcome in this first genetically tractable mouse model expressing invertebrate alternative oxidase, AOX, which can suppress pathological stresses in the mitochondrial respiratory chain.
- Subjects :
- 0301 basic medicine
RNA, Untranslated
Respiratory chain
Medicine (miscellaneous)
Physiology
lcsh:Medicine
ALTERNATIVE-OXIDASE
Mitochondrion
Immunology and Microbiology (miscellaneous)
Mitochondria
Mitochondrial disease
Alternative oxidase
Physiological Phenomena
Plant Proteins
ACUTE LETHALITY
biology
DEFECTS
Ciona intestinalis
DEFICIENCY
DROSOPHILA
Mitochondrial respiratory chain
NATIVE ELECTROPHORESIS
Biochemistry
Oxidoreductases
Research Article
lcsh:RB1-214
Biolääketieteet - Biomedicine
Transgene
Mitochondrial Disease
Respiratory Chain
Alternative Oxidase
Neuroscience (miscellaneous)
Mice, Transgenic
Protective Agents
General Biochemistry, Genetics and Molecular Biology
Mitochondrial Proteins
PROTEIN COMPLEXES
03 medical and health sciences
medicine
Metabolome
lcsh:Pathology
Animals
ddc:610
Cyanides
HUMAN-CELLS
lcsh:R
biology.organism_classification
medicine.disease
MICE
030104 developmental biology
1182 Biochemistry, cell and molecular biology
3111 Biomedicine
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Disease Models & Mechanisms, Vol 10, Iss 2, Pp 163-171 (2017), Disease models & mechanisms, 10(2): 163-171, Disease Models & Mechanisms, Dis. Model. Mech. 10, 163-171 (2017)
- Accession number :
- edsair.doi.dedup.....932cee2f61f1e1333fa77f49c3a6201f