| Research Abstract |
We have found three mitochondrial DNA mutations associated with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) (Nature 1990 ; 348 : 651-3, Biochim Biophy Acta 1991 ; 1097 : 238-240, Biochem Biophys Res Commun 1994 ; 202 : 1624-30). All the three mutations are located within the same mitochondrial leucyl transfer RNA gene, suggesting that there is a close relationship between the gene and MELAS phenotype. Because the mechanism of the pathogenesis remains to be clucidated, it is neceassary to construct an in vitro system that enables to express the mitochondrial DNA.
The 3243 mutation, which1 is present in 80% of MELAS patients, has been recognized in families with maternally transmitted diabetes mellitus (N Engl J Med 1994 ; 330 : 962-8). This may show an unexpected expansion of mitochondrial disorders. It turns out that the relationship between genetype and phenotype in mitochondrial gene disorders is more complex than that in nuclear gene disorders.
We could not develop a transgenic mouse harboring mitochondrial DNA mutation because of failure to introduce mutant genomes into mitochondria in germ cells. Since there were also many unkown matters relevant to basic mechanisms of mitochondrial biogenesis, we could not operate the same system used in nuclear gene. It needs a novel method that can overcome this problem.
|
