Charcot-Marie-Tooth–Linked Mutant GARS Is Toxic to Peripheral Neurons Independent of Wild-Type GARS Levels
Figure 6
Transgenes A and D restore viability to C201R/XM256 mice.
Motor and sensory branches of the femoral nerves of rescued C201R/XM256; Tg mice were isolated at 8 weeks of age and compared to littermate wild-type, XM256/+, and C201R/+ control mice. Toluidine blue stained sections show that motor and sensory nerves from wild type (A, B) and XM256/+ mice (C, D) control mice are qualitatively similar to nerves from C201R/+ (E, F), C201R/XM256; TgA (G, H), and C201R/XM256; TgD (I, J) mice. (K) Functionally, nerve conduction velocities in wild type and XM256/+ are not significantly different (35.2±3.4 (n = 7), and 35.5±4.2 (n = 4), respectively). However, as anticipated, values are reduced in C201R/+ mice (20.5±1.9 (n = 6), p<0.001). Conduction velocities in rescued C201R/XM256 mice were not significantly different than C201R/+ mice, but still significantly reduced compared to wild type controls (p<0.001). Values were: C201R/XM256;TgA = 25.7±0.9 (n = 4) and C201R/XM256;TgD = 20.9±2.7 (n = 3). (L) Axon numbers in the motor branch of the femoral nerve were as follows: wild type = 575±17 (n = 17), XM256/+ = 573±34 (n = 6), C201R/+ = 566±59 (n = 6), C201R/XM256;TgA = 564±14 (n = 6), C201R/XM256;TgD = 546±17 (n = 4). There were no significant differences in these values. Axon numbers in the sensory branch of the femoral nerve were also unchanged between genotypes as follows: wild type = 876±50, XM256/+ = 859±32, C201R/+ = 830±89, C201R/XM256;TgA = 822±49, C201R/XM256;TgD = 803±42. Animal numbers are the same as for motor axons except for wild type, where n = 7.