Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain

Neurofibromatosis type 1 (NF1) is a prevalent genetic disorder that affects growth properties of neural-crest-derived cell populations. In addition, a pproximately one-half of NF1 patients exhibit learning disabilities. To cha racterize NF1 function both in vitro and in vivo, we circumvent the embryon ic lethality of NF1 null mouse embryos by generating a conditional mutation in the NF1 gene using Cre/loxP technology. Introduction of a Synapsin I pr omoter driven Cre transgenic mouse strain into the conditional NF1 backgrou nd has ablated NF1 function in most differentiated neuronal populations. Th ese mice have abnormal development of the cerebral cortex, which suggests t hat NF1 has an indispensable role in this aspect of CNS development. Furthe rmore, although they are tumor free, these mice display extensive astroglio sis in the absence of conspicuous neurodegeneration or microgliosis. These results indicate that NF1-deficient neurons are capable of inducing reactiv e astrogliosis via a non-cell autonomous mechanism.