• Duchenne muscular dystrophy (DMD) is a severe, progressive, muscle-wasting disease that leads to difficulties with movement and premature death.
• Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene. These mutations frequently entail deletions of one or more exons, which disrupt the open reading frame and introduce a premature stop codon. This leads to the production of a nonfunctional truncated dystrophin protein, resulting in a severe muscle degeneration phenotype.
• The exons 4-19 of mouse Tfr1 gene that encode extracellular domain are replaced by human counterparts in B-hTFR1, Dmd KO(del45-50) mice. The genomic region of mouse Tfr1 gene that encodes cytoplasmic portion is retained. The promoter, 5’UTR and 3’UTR region of the mouse gene are also retained. The chimeric TFR1 expression is driven by endogenous mouse Tfr1 promoter, while mouse Tfr1 gene transcription and translation will be disrupted. The exons 45-50 of mouse Dmd gene were deleted in B-hTFR1, Dmd KO(del45-50) mice.
• The forelimb strength in homozygous B-hTFR1, Dmd KO(del45-50) mice was significant weaker than that in wild-type control mice, and the latency to fall, rodspeed and total distance in rotarod tests were significantly decreased in homozygous B-hTFR1, Dmd KO(del45-50) mice, showing the impairment of motor coordination and balance in homozygous B-hTFR1, Dmd KO(del45-50) mice. Gastrocnemius and soleus muscle from homozygous B-hTFR1, Dmd KO(del45-50) mice also displayed inflammation and central nuclei.
• This product is used for pharmacodynamics of Duchenne muscular dystrophy.

Gene targeting strategy for B-hTFR1, Dmd KO(del45-50) mice. The exons 4-19 of mouse Tfr1 gene that encode extracellular domain are replaced by human counterparts in B-hTFR1, Dmd KO(del45-50) mice. The genomic region of mouse Tfr1 gene that encodes cytoplasmic portion is retained. The promoter, 5’UTR and 3’UTR region of the mouse gene are also retained. The chimeric TFR1 expression is driven by endogenous mouse Tfr1 promoter, while mouse Tfr1 gene transcription and translation will be disrupted. The exons 45-50 of mouse Dmd gene were deleted in B-hTFR1, Dmd KO(del45-50) mice.

Behavioral performance in wild-type C57BL/6JNifdc and homozygous B-hTFR1, Dmd KO(del45-50) mice. Grip strength tests were conducted to assay the behavioral performance in wild-type C57BL/6JNifdc and homozygous B-hTFR1, Dmd KO(del45-50) mice (male, 3-month-old, n=12). Grip strength results showed the strength produced by forelimb was ~27.8 N/kg in homozygous B-hTFR1, Dmd KO(del45-50) mice, which was significant weaker than that in wild-type control mice. All grip strength measurements are normalized to the individual animal’s body weight. Values are expressed as mean ± SEM. Significance was determined by unpaired t test.  *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

Behavioral performance in wild-type C57BL/6JNifdc and homozygous B-hTFR1, Dmd KO(del45-50) mice. Rotarod tests were conducted to assay the behavioral performance in wild-type C57BL/6JNifdc and homozygous B-hTFR1, Dmd KO(del45-50) mice (male, 3-month-old, n=12). Rotarod tests were performed to assay the motor coordination. The latency to fall, rodspeed and total distance were significantly decreased in homozygous B-hTFR1, Dmd KO(del45-50) mice, showing the impairment of motor coordination and balance. Values are expressed as mean ± SEM. Significance was determined by unpaired t test.  *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. 

Representative histological images of skeletal muscle from wild-type C57BL/6JNifdc and homozygous B-hTFR1, Dmd KO(del45-50) mice. Gastrocnemius and soleus muscle sections from 3-month-old wild-type C57BL/6JNifdc and homozygous B-hTFR1, Dmd KO(del45-50) mice were presented to display histopathological phenotypes. Gastrocnemius and soleus muscle were stained with hematoxylin and eosin (H&E). Tissue histology was normal for wild-type control mice, but the muscle from homozygous B-hTFR1, Dmd KO(del45-50) mice displayed inflammation (red arrow) and centrally-located nuclei (black arrow).