• The DMPK gene is mainly expressed in skeletal muscle, heart, brain and several other tissues. In these tissues, DMPK is involved in the normal function and regulation of muscles. Myotonic dystrophy type 1 (DM1) is caused by the expansion of CTG nucleotide repeats in the DMPK gene. Normally, the number of CTG repeats ranges from 5 to 37 times, but in patients with DM1, this repeat can increase to several hundreds or even thousands of times.
• Gene editing strategy: The exons 1~15 of mouse Dmpk gene that encode the full-length protein were replaced by human DMPK exons 1~15 in B-hDMPK mice. The promoter, 5’UTR and 3’UTR region of the mouse gene were replaced by human counterparts.
• mRNA expression analysis: Mouse Dmpk mRNA was detectable in wild-type C57BL/6JNifdc mice. Human DMPK mRNA was detectable only in homozygous B-hDMPK mice but not in wild-type mice.
• Protein expression analysis: DMPK was detectable in heart, muscle, cortex and cerebellum of both homozygous B-hDMPK mice and wild-type C57BL/6JNifdc mice.
• Application: This product is used for pharmacodynamics and safety evaluation of Myotonic dystrophy type 1 (DM1).

Gene targeting strategy for B-hDMPK mice. The exons 1~15 of mouse Dmpk gene that encode the full-length protein were replaced by human DMPK exons 1~15 in B-hDMPK mice. The promoter, 5’UTR and 3’UTR region of the mouse gene were replaced by human counterparts.

Strain specific analysis of DMPK mRNA expression in wild-type C57BL/6JNifdc mice and homozygous B-hDMPK mice by RT-PCR. Muscle RNA was isolated from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hDMPK mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human DMPK primers. Mouse Dmpk mRNA was only detectable in wild-type C57BL/6JNifdc mice. Human DMPK mRNA was detectable only in homozygous B-hDMPK mice but not in wild-type mice.

Western blot analysis of DMPK protein expression in homozygous B-hDMPK mice. Various tissue lysates were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hDMPK mice (H/H), and then analyzed by western blot with species-specific anti-human DMPK antibody (abcam, ab102804). 50 μg total proteins were loaded for western blotting analysis. Due to antibody cross-recognition, DMPK was detectable in heart, muscle, cortex and cerebellum of both homozygous B-hDMPK mice and wild-type C57BL/6JNifdc mice.