The Next Generation of Mouse Model Preparation Platform
DMDhE45delE44
| Strain Name | C57BL/6N-DMD<sup>hE45delE44</sup> |
|---|
Exon Skipping Therapy Evaluation
Small Molecule Drug and Antioxidant/Anti-inflammatory Treatment Screening
Pharmacokinetic/Pharmacodynamic (PK/PD) Studies
CRISPR/Cas9 Gene Editing Therapeutic Research
Biomarker Screening and Validation
Traditional DMD mouse models (such as the classic mdx mice) cannot be directly used to test gene therapies designed for human genes (such as ASO antisense oligonucleotides or CRISPR base editors) due to species differences between mouse and human DMD gene sequences. Velogene replaced key parts of the mouse Dmd gene with homologous sequences of the human DMD gene by knocking out mouse exon 44 (delE44) while replacing mouse exon 45 and its adjacent intron sequence with humanized sequences (hE45), thereby constructing a gene-edited mouse model of Dmd-delE44hE45 that precisely replicates the human DMD exon 44/45 hotspot mutation region and expresses partially humanized dystrophin. Transcript amplicon sequencing showed that mouse Dmd exon 43, human DMD exon 45, and mouse Dmd exon 46 were correctly spliced together.
High Simulation of Clinically Common Mutations: About 47% of DMD patients have mutations concentrated in the exon 45–55 region, and exon 44 deletion is one of the high-frequency mutations in human DMD. This model replaces the relevant region of the mouse Dmd gene in situ with a humanized DMD sequence carrying the human exon 44 deletion (delE44), highly restoring the patient’s genetic mutation background.
Humanized Sequence Enhances Drug Translational Value: Unlike traditional mdx mice (Exon 23 mutation), which differ significantly from human mutation hotspot regions and sequences, this model introduces hotspot regions and flanking intron sequences of the human DMD gene, allowing ASOs (antisense oligonucleotides), siRNAs, or CRISPR guide RNAs designed for human-specific sequences to be effectively tested in mice, significantly improving the translatability of preclinical data.
Recapitulation of Typical DMD Pathological Phenotypes: Under the mdx or humanized background, the model exhibits prominent muscle atrophy and degeneration features, including significantly elevated serum creatine kinase (CK) activity, skeletal and cardiac muscle fibrosis, increased centrally nucleated muscle fibers, as well as functional deficits such as decreased limb grip strength and motor coordination impairment, consistent with the natural history of DMD disease progression.
Genetic Stability and In-Situ Expression: Using an in-situ knock-in strategy, the human DMD gene is expressed under the control of the mouse endogenous promoter, with a defined copy number and stable inheritance, avoiding expression level fluctuations and position effects caused by random transgenesis.
Applicability to Multidimensional Mechanism Research: It can be used for histopathological evaluation of skeletal and cardiac muscle, as well as for evaluating multi-level pharmacodynamic endpoints such as exon skipping efficiency, protein restoration levels, and motor function improvement, serving as an ideal preclinical platform bridging basic research and clinical translation.
FAQ
Game-changing benefits？
While competitors highlight germline efficiency gains, shorter timelines and enhanced 3Rs animal welfare benefits for their technologies, these are merely incremental improvements over traditional approaches. In sharp contrast, our proprietary technology delivers fully pure, homogeneous lineages—every single cell of the mice is derived exclusively from totipotent ES cells, with guaranteed 100% germline transmission efficiency. To experience these unparalleled benefits firsthand, enquire about your custom mouse model project with us or order embryos for in-house validation at your facility.
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Who owns the mouse lP? Do l need a licence from Mingceler?
All model generation projects of Mingceler operate under a fee-for-service framework.
IP Ownership: All intellectual property rights related to custom mouse models, including derived organs, tissues, cells, and biological materials, are the sole and exclusive property of the Client.
Third-Party Transfer Permission: The Client may independently decide to retain, utilize, or commercialize their custom models project materials (e.g., targeting vectors, ES cells, mouse lines) without the need for prior consent from Mingceler.
Licensing Exemption: The Client has full autonomy over all uses of the custom models or their derivatives, including but not limited to commercialization, distribution to third parties, and publication involving model data. No written license from Mingceler is required for such uses.