In the brain, Glud1-encoded glutamate dehydrogenase plays a major role in the recycling of the neurotransmitter glutamate. We recently reported a new model of brain-specific Glud1 null mice (Cns-Glud1 (-/-)) lacking glutamate dehydrogenase in the central nervous system. Cns-Glud1 (-/-) mice exhibit reduced astrocytic glutamate breakdown and redirection of glutamate pathways without altering synaptic transmission. Cns-Glud1 (-/-) mice were generated using LoxP and Nestin-Cre technology. Nestin-Cre mice are widely used to investigate gene deletion in the central nervous system. However, the Nes-Cre transgene itself was reported to induce a phenotype related to body weight gain. Here, we review the potential side-effects of Nes-Cre and analysed Cns-Glud1 (-/-) body weight gain. Overall, Nestin-Cre mice may exhibit transient and moderate growth retardation during the few weeks immediately following weaning. Pending appropriate controls and homogenization of the genetic background, Nestin-Cre technology is a valuable tool enabling disruption of genes of interest in the central nervous system.