Overactivation of mTORC1 caused by TSC1 ablation leads to hypomyelination. A, Regulatory elements of the CNP promoter drive the expression of Cre in oligodendrocytes. Schematics map of the TSC1 allele depicts the location of loxP sequences. B, Microdissected fragments of the spinal cord white matter were analyzed by Western blot to confirm TSC1 loss in conditional knock-outs. C, Higher g-ratio values of TSC1 mutants in the spinal cord ventral funiculi indicate hypomyelination compared with controls. Shown are scatter plot graphics of single fiber measurements detailing the thinner myelin in TSC1 mutants (black squares) compared with littermate controls (red circles). D, Spinal cord lysates of TSC1 mutants revealed strongly reduced levels of the myelin proteins MBP, MOG, MAG, and PLP. E, qRT-PCR revealed reduced levels of the myelin proteins MOG, MAG, and PLP in the TSC1 mutants compared with controls, whereas MBP was unchanged. F, qRT-PCR of transcripts encoding SOX 10, MRF, and Olig2 showed significant reductions in the spinal cord of TSC1 mutants. YY1 mRNA levels did not change.