Paediatric glioblastoma, also known as diffuse intrinsic pontine glioma (DIPG), affects children between 5-9 years of age and is always fatal. The disease is very strongly associated with two concurrent mutations: a K27M amino acid substitution in the histone variant H3.3, and deactivating mutations in TRP53. In an attempt to make a preclinical model of the disease we are building a mouse model in which these two mutations can be conditionally induced in the neonatal mouse brain. Our H3.3 conditional mutation is engineered so that expression of the wild-type K27-encoding transcript is substituted by the mutant M27-encoding transcript on exposure to Cre recombinase. When expression of the mutant transcript is induced by a nestin-cre transgene, we obtain an unexpected affect on growth: mice develop as dwarfs postnatally, being proportionally 65% of normal size. Liver STAT5 signalling is normal, indicating that the phenotype is not caused by a disruption of growth hormone activity regulated by the hypothalamus.