[DM pathogenesis and expansion of CTG trinucleotide repeat within 3' untranslated region of DMPK gene].
Although the expansion of an unstable CTG repeat is known to be responsible for myotonic dystrophy (DM), the mechanism by which this genetic defect induces the disease has not yet been elucidated. In patients with DM, low expression of total DM protein kinase (DMPK) and equal expression of each allele were confirmed. These result suggest that the gene product of expanded allele of DMPK causes a cis- and trans-effect on DMPK or other genes. On the other hand, existence of CUG repeat binding proteins (BP) in the nucleus of cells were reported. These CUG-BP complex may form an aggregation in the nucleus, which probably works as an inhibitory factor for the nuclear cytoplasmic transport of mRNA. All of these considerations reveal the gain-of-function model of DM, but still leave room for many more question to be answer.
Takahashi
N
N
Department of Molecular Biology, University of Tokyo.
Ishiura
S
S
D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009223:Myotonic Dystrophy / Q000235:genetics*; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics*
C585517:DMPK protein, human; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases