The DMPK gene provides instructions for producing dystrophia myotonica protein kinase, a serine/threonine kinase that is primarily expressed in skeletal muscle, cardiac muscle, and the central nervous system, with lower levels found in smooth muscle and other tissues. This protein serves as a critical regulator of cellular processes, including the maintenance of muscle structure, ion channel gating (specifically sodium and calcium channels), and intracellular signaling pathways related to cytoskeletal dynamics and mitochondrial health. The gene is famously associated with Myotonic Dystrophy Type 1 (DM1), a multisystemic disorder caused by an unstable CTG trinucleotide repeat expansion in the 3' untranslated region (3'UTR) ^[1]. In healthy individuals, this sequence repeats between 5 and 37 times, but pathogenic expansions exceeding 50 repeats—sometimes reaching thousands—lead to the production of toxic "gain-of-function" RNA ^[2]. This mutant RNA accumulates in nuclear foci, sequestering critical splicing proteins (like MBNL1) and resulting in a wide array of clinical features, including progressive muscle wasting, myotonia (the inability to relax muscles), cardiac conduction defects, cataracts, and endocrine dysfunctions such as insulin resistance ^[3].

The B6-huDMPK mouse is a humanized model constructed through gene-editing technology, in which the sequences upstream of exon 1 to intron 10 of the mouse Dmpk gene are replaced with the sequences from upstream of exon 1 to downstream of the human DMPK gene. This model can be used for research on Myotonic Dystrophy Type 1 (DM1), cardiac conduction defects, cataracts, and endocrine dysfunctions such as insulin resistance, as well as for screening, development, and preclinical evaluation of DMPK-targeted therapeutics.