Abstract: The present invention relates to the engineering an animal model, preferably mammalian models, more preferably a rat model representing Charcot-Marie-Tooth disease 2A (CMT2A) harboring the p.Arg364Trp or p.His361Tyr Mfn2 mutation, whose human counterpart results in a severe, early-onset axonal neuropathy. A model having the p.Arg364Trp Mfn2 mutation is based on a mutation made using zinc finger endonuclease technology in fertilized rat eggs. Cohorts of mutants and wild type littermates were characterized behaviorally and shown to develop multiple motor deficits that worsened over time. Separate cohorts of mutant and wild type rats sacrificed at 7, 40, and 48 weeks and analyzed by light microscopy showed a reduced density of myelinated axons and active axonal degeneration in distal but not proximal nerves, as well as axonal degeneration in the fasciculus gracilis of the cervical spinal cord at 40 and 48 weeks.

Abstract: An inactive CRISPR/Cas system-based fusion protein and its applications in gene editing are disclosed. More particularly, chimeric fusion proteins including an inCas fused to a DNA modifying enzyme and methods of using the chimeric fusion proteins in gene editing are disclosed. The methods can be used to induce double-strand breaks and single-strand nicks in target DNAs, to generate gene disruptions, deletions, point mutations, gene replacements, insertions, inversions and other modifications of a genomic DNA within cells and organisms.

Abstract: The present invention provides a method of determining the status of a multiple sclerosis patient, i.e., predicting the transition from a status of relapsing-remitting to a progressive phase of multiple sclerosis, comprising the step of measuring the amount of urinary p-cresol sulfate in the patient. The present invention also provides a method of determining the amount of lesions and total lesion area of a multiple sclerosis patient, comprising the step of measuring the amount of urinary p-cresol sulfate in the patient. Further provided is a method of monitoring myelination in a developing child, comprising the step of: measuring the amount of p-cresol sulfate in the urine of said child.

Abstract: The present invention provides a method of determining the status of a multiple sclerosis patient, i.e., predicting the transition from a status of relapsing-remitting to a progressive phase of multiple sclerosis, comprising the step of measuring the levels of urinary myelin basic protein-like material in the patient. The present invention also provides a method of determining the amount of lesions and total lesion area of a multiple sclerosis patient, comprising the step of measuring the levels of urinary myelin basic protein-like material in the patient. Further provided is a method of monitoring myelination in a developing child, comprising the step of: measuring the levels of myelin basic protein-like material in the urine of said child.