Table 2 List of mouse models for NFs and other neuronal intermediate proteins
Protein | Gene | Protein expression levels compared to wild type | Promoter | Phenotype | Reference |
|---|---|---|---|---|---|
NF-H | NEFH | Overexpression (2-fold) | Human NEFH promoter with regulatory elements (full genomic region) | NF accumulation, axonal transport disruption, selective motor neuron degeneration | [72] |
Nefh | 50–70% increase over endogenous NF-H levels | Mouse Nefh promoter with regulatory elements (full genomic region) | No overt phenotype, slower axonal transport, reduced axonal diameter | [73] | |
Nefh/LacZ fusion gene | Less than 10% as compared to endogenous NF-L levels | Mouse Nefh promoter | No overt phenotype, NF accumulation | [74] | |
Nefh lacking the C-terminal 612 amino acids | Similar to endogenous NF-H levels | Mouse Nefh promoter | No overt phenotype | [75] | |
NF-M | NEFM | Overexpression (2- to 4-fold) | Human NEFM promoter with regulatory elements (full genomic region) | NF accumulation, axonal loss, progressive hind limb paralysis | [76] |
NEFM | 3–25% of endogenous NF-M levels | Human NEFM promoter with regulatory elements (full genomic region) | No overt phenotype, NF accumulation | [77] | |
NEFM | 2–25% of endogenous NF-M levels | Human NEFM promoter with regulatory elements (full genomic region) | No overt phenotype, NF accumulation | [78] | |
NEFM fused to a 11 amino acid tag | Brain region specific expression patterns | Human NEFM promoter | No overt phenotype | [79] | |
NEFM lacking the multi-phosphorylation region (MPR) | Brain region specific expression patterns (100% of endogenous NF-M in cortex and hippocampus) | Human NEFM promoter | No overt phenotype | [80] | |
Nefm lacking the C-terminal 50 amino acids | Overexpression (2-fold) | Murine sarcoma virus (MSV) promoter | No overt phenotype, NF accumulation, axonal radial growth inhibition | [81] | |
Nefm KSP phospho-incompetent | Endogenous levels | Mouse Nefm promoter | No phenotype | [59] | |
Nefm lacking the C-terminal 426 amino acids | Similar levels of endogenous NF-M | Mouse Nefm promoter | No overt phenotype, axonal radial growth inhibition | [82] | |
NF-L | Nefl | Overexpression (2-fold) | Murine sarcoma virus (MSV) promoter | No overt phenotype, cataract formation | [83] |
Nefl | Overexpression (4-fold) | Murine sarcoma virus (MSV) promoter | NF accumulation, axonal degeneration, axon swelling, severe skeletal muscle atrophy | [84] | |
L394P Nefl | 50% of endogenous NF-L | Murine sarcoma virus (MSV) promoter | NF accumulation, selective motor neuron degeneration, severe skeletal muscle atrophy | [85] | |
P22S NEFL | 1.4 times of endogenous NF-L | Thy1 Tet-Off promoter | Gait anomalies, sensimotor deficits, loss of muscle innervation | [86] | |
N98S Nefl | 30% less of total NF-L | Endogenous Nefl promoter (knock-in) | Abnormal hindlimb posture, tremor, disorganized processes in cerebellum and cortex, lower levels of NFs, reduced axonal diameter, NF aggregates | [87] | |
P8R Nefl | 50–60% less of total NF-L | Endogenous Nefl promoter (knock-in) | No phenotype | [87] | |
Peripherin | Prph | Overexpression (2 to 7-fold, according to the region) | human Thy1 gene promoter | Selective degeneration of motor axons during aging | [88] |
INA | Ina (rat) | Overexpression (3-fold) | Rat Ina promoter with regulatory elements (full genomic region) | Motor coordination deficits, neuronal IF accumulations | [89] |