PI3K/AKT signaling participates in Nbs1‐mediated controlling the size of cerebral cortex

Nijmegen breakage syndrome (NBS) is an autosomal recessive genetic disease. NBS gene (known as Nbn in mouse) product Nbs1, is a predominant component of MRN complex (Mre11/Rad50/Nbs1) that participates actively in DNA damage repair. All NBS patients show microcephaly, suggesting Nbs1 may have a special role in controlling the size of brain. We have shown previously that mice with neuronal specific disruption of Nbn gene (Nbn‐CNS‐del) displayed ataxia and microcephaly. Further morphological analysis showed neuronal atrophy¡¢myelination defects in Nbn‐CNS‐del cortex. As PI3K/AKT/mTOR signaling pathway can promote survival¡¢proliferation¡¢migration¡¢and protein synthesis of neurons, to explore the molecular mechanisms of these abnormal changes in Nbn‐CNS‐del mice, we have analysed the PI3K/AKT/mTOR pathway in the cerebral cortex of different aged Nbn‐CNS‐del mice and age matched control mice. We found that Nbs1 deficiency decreased the gene expression levels of PI3K, AKT, and mTOR in the cerebral cortex compared to that in age matched control mice. These changes could be detected at early postnatal stages. These results demonstrated that neuronal specific deficiency of Nbs1 severely affected the vitality of PI3K/AKT/mTOR signaling pathway in the cerebral cortex.