Key result
Mice carrying multigene mutations in Dmpk, Six5, Mbnl1, and Dmwd recapitulate major manifestations of adult-onset and congenital myotonic dystrophy type 1.
Why the study?
Multisystem manifestations in DM1 may involve dosage reduction in multiple genes, but direct evidence was lacking.
Answers are grounded in this paper and cite their sources.
The complex symptoms of myotonic dystrophy type 1 likely result from the reduced gene dosage of multiple genes, as demonstrated in novel multigene mutant mouse models.
Multisystem manifestations in myotonic dystrophy type 1 (DM1) may be due to dosage reduction in multiple genes induced by aberrant expansion of CTG repeats in DMPK, including Dmpk and its neighboring genes (Six5 or Dmwd) and downstream Mbnl1. However, the direct evidences are lack. Here, we develop a new strategy to generate mice carrying multigene mutations in one step by injection of haploid embryonic stem cells with mutant Dmpk, Six5 and Mbnl1 into oocytes. The triple heterozygous mutant mice exhibit adult-onset DM1 phenotypes. With the additional mutation in Dmwd, quadruple heterozygous mutant mice recapitulate many major manifestations in congenital DM1. Moreover, muscle stem cells in both models display reduced stemness. Our results suggest that the complex symptoms of DM1 result from the reduced gene dosage of multiple genes.
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Yin et al. (2019) studied Myotonic dystrophy type 1. Multigene mutations (Dmpk, Six5, Mbnl1, and Dmwd) was evaluated on Phenotypic manifestations of DM1 and muscle stem cell stemness. Mice carrying multigene mutations in Dmpk, Six5, Mbnl1, and Dmwd recapitulate major manifestations of adult-onset and congenital myotonic dystrophy type 1.
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