Dosage effect of multiple genes accounts for multisystem disorder of myotonic dystrophy type 1

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 , its neighboring genes ( SIX5 or DMWD ) and downstream MBNL1 . However, direct evidence is lacking. Here, we develop a new strategy to generate mice carrying multigene heterozygous mutations to mimic dosage reduction in one step by injection of haploid embryonic stem...