The heterozygous, neomorphic mutation of isocitrate dehydrogenase 1 (IDH1) in glioma results in the generation of D-2-hydroxyglutarate, a proposed oncometabolite. A brain-specific (nestin–Cre) knock-in of one allele of Idh1 with an R132H mutation results in high levels of neuronal apoptosis, haemorrhage and perinatal lethality. This is associated with the inhibition of collagen prolyl hydroxylases, which leads to the loss of collagen maturation and basement membrane disruption. A few GFAP-Cre mice survive Idh1 R132H expression but do not develop glioma. This suggests that IDH1 mutation promotes glioma genesis only in the context of other mutations.