Table 2. Characteristics of murine models, muscle histology and immune response after injections.
| Mice | Main features |
Muscle histology after PBS i.m. injection |
Muscle histology after SGCA-HY i.m. gene transfer |
Transgene expression in the muscle after gene transfer | Antitransgene IR after gene transfer | ||
|---|---|---|---|---|---|---|---|
| Centronucleated fibersa | Cellular infiltratesb | Centronucleated fibersa | Cellular infiltratesb | ||||
| C57BL/6 | Control; CD45.2 congenic mice | 0 | 0 | ++++ | +++ CD3, CD4, CD8 and CD11b cells | Lost after 14 days, but maintained with miR142-regulated vector | Strong CD4 and CD8 IR. IR is prevented with miR142-regulated vector |
| Sgca-/- | Homozygous null for Sgca; LGMD2D pathologic model | +++ | + | ++++ | +++ CD3, CD4, CD8 and CD11b cells | Lost after 14 days, but prolonged with miR142-regulated vector | Strong CD4 and CD8 IR. IR is partially controlled with miR142-regulated vector |
| CD4-/- | Homozygous null for CD4; lack CD4+ T cells | 0 | 0 | 0 | 0 | Maintained | No CD4 or CD8 IR |
| CD8-/- | Homozygous null for CD8a; lack CD8+ T cells | 0 | 0 | +++ | ++ CD3, CD4 and CD11b cells | Lost after 14 days | Strong CD4 IR, no CD8 IR |
| CD4-/- Sgca-/- | Null for CD4 and sgca genes; lack CD4+ T cells | +++ | + | +++ | + CD11b cells | Maintained | No CD4 or CD8 IR |
| CD8-/- Sgca-/- | Null for CD8a and sgca genes; lack CD8+ T cells | +++ | + | ++++ | ++ CD3, CD4 and CD11b cells | Lost after 14 days | Strong CD4 IR, no CD8 IR |
| MHC II-/- | Homozygous null for MHC cl II genes; lack CD4+ T cells | 0 | 0 | 0 | 0 | Maintained | No CD4 or CD8 IR |
| β2M-/- | Homozygous null for B2M microglobulin; lack MHC cl I and CD8+ T cells | 0 | 0 | ++++ | ++ | Lost after 14 days | Strong CD4 IR, no CD8 IR |
| μMT -/- | IghM-targeted mutation; lack mature B cells | 0 | 0 | ++++ | +++ | Lost after 14 days | Strong CD4 and CD8 IR |
Abbreviations: β2M, β2-microglobulin; Ig, immunoglobulin G; IR, immune response; MHC cl, major histocompatibility complex class; TA, tibialis anterior.
a
Estimated percentages of centronucleated fibers among fibers of representative muscle sections: 0=<5% ++=50–70% +++=70–80% ++++=>90%.
b
Cellular infiltration in the injected TA was estimated as: 0=none;+= mild; ++=moderate; +++=strong.