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Table 2 List of mouse models for NFs and other neuronal intermediate proteins

From: The role of neurofilament aggregation in neurodegeneration: lessons from rare inherited neurological disorders

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]