Animal models for demyelination disorders

A method of reducing neuronal demyelination comprising administering to a myelinating cell an effective amount of a small molecule, wherein said small molecule reduces neuronal demyelination when administered to a transgenic mouse whose genome comprises:

• (a) a stably integrated transgenic nucleotide sequence encoding interferon-gamma (IFN-γ) operably linked to an inducible promoter;
• and
• (b) a heterozygous knock-out of the endogenous pancreatic endoplasmic reticulum (ER) kinase gene (PERK), wherein upon expression of said IFN-γ, said transgenic mouse exhibits a greater degree of demyelination relative to a transgenic mouse having a stably integrated transgenic nucleotide sequence encoding IFN-γ as in (a), but lacking said heterozygous knock-out of the PERK gene,
• wherein said small molecule is characterized in that upon said administration and upon said expression of said IFN-γ in said transgenic mouse neuronal demyelination is reduced, and wherein said small molecule is effective to decrease growth and DNA damage protein 34 (GADD34) activity or increase pancreatic ER kinase (PERK) activity, resulting in an increase of phosphorylated eukaryotic translation initiation factor 2 alpha (p-eIF-2α) inside said myelinating cell.