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Publication : Neuropathological signatures revealed by transcriptomic and proteomic analysis in Pten-deficient mouse models.

First Author  Cheung SKK Year  2023
Journal  Sci Rep Volume  13
Issue  1 Pages  6763
PubMed ID  37185447 Mgi Jnum  J:357337
Mgi Id  MGI:7483924 Doi  10.1038/s41598-023-33869-7
Citation  Cheung SKK, et al. (2023) Neuropathological signatures revealed by transcriptomic and proteomic analysis in Pten-deficient mouse models. Sci Rep 13(1):6763
abstractText  PTEN hamartoma tumour syndrome is characterised by mutations in the human PTEN gene. We performed transcriptomic and proteomic analyses of neural tissues and primary cultures from heterozygous and homozygous Pten-knockout mice. The somatosensory cortex of heterozygous Pten-knockout mice was enriched in immune response and oligodendrocyte development Gene Ontology (GO) terms. Parallel proteomic analysis revealed differentially expressed proteins (DEPs) related to dendritic spine development, keratinisation and hamartoma signatures. However, primary astrocytes (ASTs) from heterozygous Pten-knockout mice were enriched in the extracellular matrix GO term, while primary cortical neurons (PCNs) were enriched in immediate-early genes. In ASTs from homozygous Pten-knockout mice, cilium-related activity was enriched, while PCNs exhibited downregulation of forebrain neuron generation and differentiation, implying an altered excitatory/inhibitory balance. By integrating DEPs with pre-filtered differentially expressed genes, we identified the enrichment of traits of intelligence, cognitive function and schizophrenia, while DEPs in ASTs were significantly associated with intelligence and depression.
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