Myotonic dystrophy type 1 (DM1) is an inherited, multi-system disorder, affecting 1 in 8,500 individuals worldwide. However, no effective therapies are currently available for this disease. Clinical symptoms may vary from almost asymptomatic to progressive skeletal muscle wasting, repetitive muscle contractions (myotonia), early onset particulate cataracts, insulin resistance and cardiomyopathy. DM1 pathogenesis is characterized by abnormal expansion of trinucleotide CTG repeat in the gene DMPK on chromosome 19. Even though the mutation responsible for the clinical manifestations of DM1 was identified in 1992, development of effective treatments still requires elucidation of molecular mechanisms.
Researchers at the University of Florida have isolated myoblasts from a Dmpk CTG480 knock-in mouse model for DM1. This cell model serves as an invaluable tool for the study of DM1 pathogenesis and as a translational platform for therapeutic drug development.
A Dmpk CTG480 knock-in mouse platform for therapeutic drug development and for elucidating molecular mechanisms for DM1
Dmpk CTG480 knock-in mice were generated using rolling circle amplification, to generate large uninterrupted CTG repeats in vitro, followed by CRISPR/Cas9 genome editing in zygotes. These mice express the CTG480 expansion mutation under the control of the Dmpk promoter and therefore are a mouse model for the neuromuscular disease myotonic dystrophy type 1, the most common form of adult-onset muscular dystrophy.
