Mice with double Mbnl1/Mbnl2 KO or Mbnl1/Mbnl3 KO exhibited more severe phenotypes compared with the single KO [59,60] and the triple Mbnl1/2/3 KO in muscle tissues recapitulated the severe phenotype observed in congenital DM1, in both newborn and adult mice [61], supporting the idea of a prominent role of MBNL proteins and alternative splicing dysregulation in DM1 pathogenesis. This evidence concerns the gene MBNL1 and myotonic dystrophy type 1.