Table 1.
Comparison between available CMT2A mouse models
| HB9 Mfn2T105M (Detmer 2008) | Eno MFN2 R94Q (Cartoni 2010) | Nestin-cre MFN2T105M (Bannerman 2016) | Thy1.2 MFN2R94Q (Zhou 2019) | ||||
|---|---|---|---|---|---|---|---|
| MFN2 mutation | T105M | R94Q | T105M | R94Q | |||
| MFN2 transgene promoter | Hb9 | Eno | Rosa-STOP-MFN2T105M/CAG-CreERT2 | Nestin-cre | Thy1.2 | ||
| Genotype | Homozygous | Heterozygous | Homozygous (MitoCharc2) | Heterozygous (MitoCharc1) | Homozygous | Heterozygous | Y-linked |
| Phenotype onset | Severe congenital | Mild congenital | Mild late | Mild late | 6 W post-tamoxifen induction | Mild late | Early |
| Motor resistance (Rotarod test) | Hindlimb muscles weakness but no alteration | No alteration | Frequent fall off | Frequent fall off | Not detectable | Not significant | Frequent fall off |
| Grip strength | / | / | / | / | / | / | Frequent fall off |
| Gait (Noldus Catwalk) | Defect in dorsi-flexion but no gaiting alteration | No alteration | Abnormal print length | No alteration | / | Abnormal print length | Progressive gaiting worsening |
| Axon (number, size, g-ratio) | 40% fewer axons in motor roots (L4 and L5) | No alteration | + 55% of < 3.5 μm axons | + 40% of < 3.5 μm axons; Aδ fibers altered in the sciatic nerves | / | No alteration | Degeneration in tibialis muscle |
| Muscle fiber | Smaller anterior hindlimb muscles | No alteration | No alteration | No alteration | / | Smaller tibialis and soleus muscles | / |
| Mitochondria (number, aggregates, axonal transport) | Highly aggregation and clusters | Highly aggregation and clusters | N° mitochondria + 28% in < 3.5 μm axons | N° mitochondria + 34% in < 3.5 μm axons | Reduced number in tibialis axons | No alteration | Clusters and morphology abnormalities. No mitophagy |
| Sensitive phenotype | / | / | / | / | / | / | / |