Table 2.
Characteristics of the various CRISPR-generated Duchenne muscular dystrophy (DMD) animal models discussed in this review.
| Animal | Study | Strain/Breed | Dystrophin Mutation | Features (In Males, Unless Specified) | Therapies Tested |
|---|---|---|---|---|---|
| Mouse | Kim et al. (2017) | C57BL6/J | Dmd ex20 point mutation (Q871Stop) | Dystrophin and nNOS absent in skeletal muscle sarcolemma | CRISPR editing of ex20 point mutation [63] |
| Amoasii et al. (2017) | C57BL6/J | Dmd ex50 deletion | Dystrophin absent in skeletal and cardiac muscles, histopathology at 3 weeks, decreased forelimb grip strength at 2 months | CRISPR reframing or skipping of ex51 [64] | |
| Young et al. (2017) | C57BL/10, DBA/2 | DMD ex45 deletion | Humanized model, dystrophin absent in skeletal and cardiac muscles on mdx and mdxD2 backgrounds, histopathology at 6 weeks on mdxD2 background | CRISPR deletion of ex45-55 [65] | |
| Koo et al. (2018) | C57BL6/J | various Dmd exon 23 indel mutations (e.g., −14bp, +1bp) | Dystrophin absent in skeletal muscles, nNOS absent in skeletal muscle sarcolemma, decreased TA-specific force at nearly 4 months | CRISPR reframing of ex23 [66] | |
| Min et al. (2019) | C57BL6/J | Dmd ex44 deletion | Dystrophin absent in skeletal and cardiac muscles, histopathology at 4 weeks, decreased EDL-specific force at 4 weeks and forelimb grip strength at 8 weeks | CRISPR reframing or skipping of ex51/53 [67] or of ex45 [68] | |
| Egorova et al. (2019) | C57BL6/J × CBA |
Dmd ex8-34 deletion | Dystrophin, DAGC members absent in skeletal muscles, histopathology at 12 weeks, decreased TA force parameters and wire hanging test performance across age (2–12 months) | None | |
| Amoasii et al. (2019) | Not indicated | Dmd ex50 deletion | Similar to those from Amoasii et al. (2017), with capability of in vivo non-invasive monitoring of dystrophin levels via luciferase expression | CRISPR reframing or skipping of ex51 [69] | |
| Rat | Nakamura et al. (2014) | Wistar-Imamichi | various Dmd exon 3 and/or 16 indel mutations | Dystrophin absent or reduced in skeletal muscle, histopathology at approximately 4 or 13 weeks for skeletal muscle and at 13 weeks for the heart, decreased wire hanging test performance | None |
| Pig | Yu et al. (2016) | Diannan miniature pig | various DMD exon 27 indel mutations | Only one mutant obtained with unspecified sex and very early mortality at 52 days post-birth, dystrophin reduced in skeletal and cardiac muscles, histopathology observed at autopsy with the heart having enlarged, discolored foci | Not applicable |
| Rabbit | Sui et al. (2018) | New Zealand | various DMD exon 51 indel mutations | Sex unspecified: reduced survival mostly by 20 weeks, dystrophin absent in skeletal and presumably cardiac muscles, histopathology at 5 months, reduced mobility at 2–3 months, decreased systolic function at 4 months | None |
| Monkey | Chen et al. (2015) | Rhesus | various DMD exon 4 and/or 46 indel mutations | Only stillborn monkeys analyzed (male and female): dystrophin reduced in muscle, histopathology observed | None |
Abbreviations: ex, exon; nNOS, neuronal nitric oxide synthase; TA, tibialis anterior; EDL, extensor digitorum longus.