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

Genes & development | Apr 1, 2001

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

Pubmed ID: 11297510 RIS Download

Mesh terms: Alleles | Animals | Cell Transformation, Neoplastic | Cells, Cultured | Cerebral Cortex | Disease Models, Animal | Ganglia, Spinal | Gene Expression Regulation, Developmental | Genes, Neurofibromatosis 1 | Genes, Reporter | Genes, Synthetic | Genetic Vectors | Gliosis | Integrases | Lac Operon | Learning Disorders | MAP Kinase Signaling System | Mice | Mice, Knockout | Mice, Neurologic Mutants | Mice, Transgenic | Nerve Tissue Proteins | Neurofibromin 1 | Neurons | Promoter Regions, Genetic | Proto-Oncogene Proteins p21(ras) | Recombinant Fusion Proteins | Signal Transduction | Synapsins | Viral Proteins | p120 GTPase Activating Protein

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Associated grants

  • Agency: NIDDK NIH HHS, Id: R01 DK048247
  • Agency: NINDS NIH HHS, Id: R01 NS034296
  • Agency: NIDDK NIH HHS, Id: DK 48247
  • Agency: NINDS NIH HHS, Id: R01-NS34296-05

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