Abstract

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.

Details

Title
Neuropathological signatures revealed by transcriptomic and proteomic analysis in Pten-deficient mouse models
Author
Cheung, Stanley K. K. 1 ; Kwok, Jacinda 2 ; Or, Penelope M. Y. 1 ; Wong, Chi Wai 3 ; Feng, Bo 1 ; Choy, Kwong Wai 4 ; Chang, Raymond C. C. 5 ; Burbach, J. Peter H. 6 ; Cheng, Alfred S. L. 1 ; Chan, Andrew M. 7 

 The Chinese University of Hong Kong, School of Biomedical Sciences, Hong Kong, China (GRID:grid.10784.3a) (ISNI:0000 0004 1937 0482) 
 The Chinese University of Hong Kong, School of Biomedical Sciences, Hong Kong, China (GRID:grid.10784.3a) (ISNI:0000 0004 1937 0482); University of Toronto, Department of Pharmaceutical Sciences, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938) 
 The Chinese University of Hong Kong, School of Biomedical Sciences, Hong Kong, China (GRID:grid.10784.3a) (ISNI:0000 0004 1937 0482); Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, Louvain-la-Neuve, Belgium (GRID:grid.7942.8) (ISNI:0000 0001 2294 713X) 
 The Chinese University of Hong Kong, Department of Obstetrics and Gynaecology, Hong Kong, China (GRID:grid.10784.3a) (ISNI:0000 0004 1937 0482) 
 The University of Hong Kong, Laboratory of Neurodegenerative Diseases, School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, Hong Kong, China (GRID:grid.194645.b) (ISNI:0000000121742757) 
 University Medical Center Utrecht, Department of Translational Neuroscience, Utrecht, The Netherlands (GRID:grid.7692.a) (ISNI:0000000090126352) 
 The Chinese University of Hong Kong, School of Biomedical Sciences, Hong Kong, China (GRID:grid.10784.3a) (ISNI:0000 0004 1937 0482); The Chinese University of Hong Kong, Brain and Mind Institute, Hong Kong, China (GRID:grid.10784.3a) (ISNI:0000 0004 1937 0482) 
Pages
6763
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2805772424
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.