Mclk1+/- mice are not resistant to the development of atherosclerosis.
BACKGROUND
Mice with a single copy of Mclk1 (a.k.a. Coq7), a gene that encodes a mitochondrial enzyme required for the biosynthesis of ubiquinone and other functions, live longer than wild-type mice. The prolonged survival implies a decreased mortality from age-dependent lethal pathologies. Atherosclerosis is one of the main age-dependent pathologies in humans and can be modeled in mice that lack Apolipoprotein E (ApoE-/-) or mice that lack the Low Density Lipoprotein Receptor (LDLr-/-) in addition to being fed an atherosclerosis-inducing diet. We sought to determine if Mclk1 heterozygosity protects against atherosclerosis and dyslipidemia in these models.


RESULTS
We found that Mclk1 heterozygosity did not protect against dyslipidemia, oxidative stress, or atherosclerosis in young (6 or 10 months) or older (18 months) mice. Furthermore, the absence of ApoE suppressed the lifespan-promoting effects of Mclk1 heterozygosity.


CONCLUSIONS
These findings indicate that although Mclk1 heterozygosity can extend lifespan of mice, it does not necessarily protect against atherosclerosis. Moreover, in the presence of hyperlipidemia and chronic inflammation, Mclk1 heterozygosity is incapable of extending lifespan.
Department of Biology, McGill University, Montreal H3A 1B1, Canada. bryan.hughes@mail.mcgill.ca
Bryan G
BG
Hughes
Siegfried
S
Hekimi
D000367:Age Factors; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D050171:Dyslipidemias / Q000235:genetics; D006579:Heterozygote; D007249:Inflammation; D008136:Longevity / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D024101:Mitochondrial Proteins; D006899:Mixed Function Oxygenases; D018384:Oxidative Stress / Q000235:genetics
D001057:Apolipoproteins E; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D006899:Mixed Function Oxygenases; C434481:Coq7 protein, mouse