Table 3.
Summary of AAV-Galgt2 intramuscular injection experiments in utrophindeficient mdx mice.
| Genotype | Age | Percent central myofiber nuclei | |||
|---|---|---|---|---|---|
| Injected | Analyzed | Muscle | CT overexpressing | Non-overexpressing | |
| 1. mdxutrn+/- | 1wk | 6wks | G | 3 | 57 |
| 2. mdxutrn+/- | 1wk | 6wks | G | 1 | 64 |
| 3. mdxutrn+/- | 1wk | 6wks | Q | 1 | 73 |
| 4. mdxutrn+/- | 1wk | 6wks | G | 1 | 63 |
| 5. mdxutrn+/- | 1wk | 6wks | G | 0 | 62 |
| 6. mdxutrn+/- | 1wk | 6wks | Q | 4 | 62 |
| 7. mdxutrn+/- | 1wk | 6wks | G | 4 | 66 |
| 8. mdxutrn+/- | 1wk | 6wks | Q | 5 | 60 |
| 9. utrn-/- | 1wk | 6wks | G | 0 | 0 |
| 10. mdxutrn-/- | 1wk | 6wks | G | 4 | 35 |
| 11. mdxutrn-/- | 1wk | 6wks | Q | 3 | 57 |
| 12. mdxutrn-/- | 1wk | 6wks | G | 5 | 63 |
| 13. mdxutrn-/- | 4d | 6wks | G | 4 | 77 |
| 14. mdxutrn-/- | 4d | 6wks | Q | 5 | 64 |
| 15. mdxutrn-/- | 4d | 6wks | G | 3 | 52 |
| 16. mdxutrn-/- | 4d | 8wks | G | 0 | 65 |
| 17. mdxutrn-/- | 1wk | 8wks | G | 0 | 86 |
| 18. mdxutrn-/- | 1wk | 8wks | G | 0 | 75 |
| Average of mdxutrn+/- 1wk | 6wks | G,Q | 2±1*** | 63±2 | |
| Average of mdxutrn-/- 4d-1wk | 6-8wks | G,Q | 3±1*** | 63±5 | |
Adeno-associated virus (AAV) serotype 1 or 8-like (rh.74) containing the CT GalNAc transferase (Galgt2) transgene was delivered by intramuscular injection at 1-2×1010vg. After 1-2 months, muscles were analyzed for CT carbohydrate overexpression and for the presence of centrally located myofiber nuclei, an indicator of dystrophic pathology. In mdx mice, dystrophic pathology begins to develop after 3 weeks of age. If transgene was delivered at 4 days (d) to 1 week (wk) of age, a highly significant reduction in pathology was observed in myofibers expressing transgene, both in mdx mice that were heterozygous for utrophin (mdxutrn+/-) and in mice that were deficient in utrophin (mdxutrn-/-). G, Gastrocnemius; Q, Quadriceps. Errors are standard deviations
P<0.001 for a 2-tailed Student’s t test.