• 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.
• B-hDMD(exon44-46, del45)/hTFR1 mice were obtained by mating B-hDMD(exon44-46, del45) mice (114088) and B-hTFR1 mice (110861).
• The exon 44, exon 45 and exon 46 of mouse Dmd are replaced by exon 44 and exon 46 of human DMD in B-hDMD(exon44-46, del45)/hTFR1 mice. The human exon 44 is flanked by ~1kb of human intron 43 and human intron 44 sequences, while human exon 46 is flanked by ~1kb of human intron 45 and human intron 46 sequences. The exons 4-19 of mouse Tfr1 gene that encode extracellular domain are replaced by human counterparts in B-hDMD(exon44-46, del45)/hTFR1 mice. The genomic region of mouse Tfr1 gene that encodes cytoplasmic portion is retained. The promoter, 5’UTR and 3’UTR 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 forelimb strength in homozygous B-hDMD(exon44-46, del45)/hTFR1 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-hDMD(exon44-46, del45)/hTFR1 mice, showing the impairment of motor coordination and balance in homozygous B-hDMD(exon44-46, del45)/hTFR1 mice.
• This product is used for pharmacodynamics of Duchenne muscular dystrophy.

Gene targeting strategy for B-hDMD(exon44-46, del45)/hTFR1 mice. The exon 44, exon 45 and exon 46 of mouse Dmd are replaced by exon 44 and exon 46 of human DMD in B-hDMD(exon44-46, del45)/hTFR1 mice. The human exon 44 is flanked by ~1kb of human intron 43 and human intron 44 sequences, while human exon 46 is flanked by ~1kb of human intron 45 and human intron 46 sequences.

The exons 4-19 of mouse Tfr1 gene that encode extracellular domain are replaced by human counterparts in B-hDMD(exon44-46, del45)/hTFR1 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.

Note: B-hDMD(exon44-46, del45)/hTFR1 mice were obtained by mating B-hDMD(exon44-46, del45) mice (114088) and B-hTFR1 mice (110861).

Behavioral performance in wild-type C57BL/6JNifdc and homozygous B-hDMD(exon44-46, del45)/hTFR1 mice. Grip strength tests were conducted to assay the behavioral performance in wild-type C57BL/6JNifdc and homozygous B-hDMD(exon44-46, del45)/hTFR1 mice (male, 6-week-old, n=12). Grip strength results showed the strength produced by forelimb was ~18.01 N/kg in homozygous B-hDMD(exon44-46, del45)/hTFR1 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-hDMD(exon44-46, del45)/hTFR1 mice. Rotarod tests were conducted to assay the behavioral performance in wild-type C57BL/6JNifdc and homozygous B-hDMD(exon44-46, del45)/hTFR1 mice (male, 6-week-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-hDMD(exon44-46, del45)/hTFR1 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.