Sport is healthy!
Exercise strengthens muscles, trains brains and enhances libido. But there's much more than that to sport! Training can even reduce severe effects of defective genes on the vascular system in mice. Housing conditions can affect the differences observed between knockout and wild-type mice, warns a new report in PloS One. By Karin Hollricher.
(Mar 2nd 2007) How environment influences the effect of gene knockouts describes Ann L. Baldwin's team from the University of Arizona in Tucson. The scientists took a close look at the function of fibulin proteins. These proteins - there are six in total - are thought to play an important function in maintaining the mechanical properties of vascular walls. Though each protein performs different functions, they are all thought to serve as molecular bridges between smooth muscle cells and surrounding extra-cellular matrix, such as elastin and collagen fibres.
Knockout of the fibulin 4 gene in mice leads to death just before birth due to arterial haemorrhaging. Heterozygous fibulin 4 knockout mice survive and appear to be phenotypically more or less healthy. However, they suffer from severe arterial pathological manifestations. Sure enough, a defective gene can never produce a correctly working protein. That is a rock solid fact. But introduce sport and the entire picture changes. Living in enriched cages prevents heterozygous fibulin 4+/- knockout mice from developing arterial malfunctions.
This stunning result is revealed only through the microscope. Heterozygous knockout animals living in standard cages develop small areas of disorganised tissue between aortic smooth muscle cells, referred to as "gaps". Baldwin detected approximately 10 times more gaps in these mice (172 gaps per square mm) than in wild-type animals (15 gaps). However, running and climbing reduced the number of gaps in the arteria of heterozygous knockout animals almost to wild-type amounts, namely to 35 gaps per square mm. The authors speculate that other members of the fibulin family may have compensated for the low level of fibulin 4 protein in heterozygous knockout mutants.
What else does the study tell us?
It's known that mental and motoric activities incite the brain's enormous plasticity. In earlier studies it has also been shown that an enriched environment alleviates and/or delays the onset of disease symptoms in mice. These studies were about neuronal diseases like Huntington, Fragile X Syndrome or Alzheimer. The Baldwin's team study, however, demonstrates for the first time a connection between a genetically determined, vascular disease and environment affecting the degree of manifestation of disease symptoms. It is interesting to note that healthy animals also benefited from sportive lifestyle. Wild-type mice growing up in enriched cages exhibited only 3 gaps per square mm compared to 15 gaps in mice living in standard cages.
The study also sheds light on the fact that scientists should pay careful attention to housing conditions and always bear in mind that differences in lifestyle could account for varying results. "Knockout Mice: Is it Just Genetics?" queries the title of the authors' paper. Based on their results one has to say "No, it's not always just genetics." Thus, research findings assumed to be attributed to genetic differences might be interpreted incorrectly, neglecting the role of environmental factors. Baldwin et al. argue that different housing conditions could, in fact, be the explanation for pathological differences in fibulin 4 mutants observed in earlier experiments.
Study to be found here
