Dataset Information

Cntnap2 KO mouse mPFC proteome for ASD

ABSTRACT: Autism Spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder where patients have impaired social behavior and communication, and restricted interests. Although various studies have been carried out to unveil the mechanisms associated with ASD, its pathophysiology is still poorly understood. Genetic variants on CNTNAP2 have been found and considered representative ASD genetic risk factors, and disruption of Cntnap2 causes ASD phenotypes in mice. Here, we performed an integrative multi-omics analysis by combining quantitative proteometabolomics data of Cntnap2 knockout (KO) mice with multi-omics data from ASD patients and forebrain organoids to elucidate Cntnap2-dependent molecular networks of ASD. First, we found Cntnap2-associated molecular signatures and cellular processes by conducting mass spectrometry-based proteometabolomic analysis of the medial prefrontal cortex of the Cntnap2 KO mouse model. Then, we narrowed these identified processes into bona fide ASD molecular processes by incorporating multi-omics data of ASD patients' prefrontal cortex. Further, we mapped cell-type-specific ASD networks by reanalyzing single-cell RNA-seq data of forebrain organoids derived from patients with CNTNAP2 mutation. Finally, we constructed a Cntnap2-associated ASD network model consisting of mitochondrial dysfunction, axonal impairment, and synaptic activity. Our results may shed light on understanding of the Cntnap2-dependent molecular networks of ASD.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: jihwan park

LAB HEAD: Min-Sik Kim

PROVIDER: PXD031656 | Pride | 2023-03-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	MSK_Cntnap2_mPFC_bRPLC_F01.mzXML	Mzxml
	MSK_Cntnap2_mPFC_bRPLC_F01.raw	Raw
	MSK_Cntnap2_mPFC_bRPLC_F01_PEMMR.mgf	Mgf
	MSK_Cntnap2_mPFC_bRPLC_F01_PEMMR.mzid.gz	Mzid
	MSK_Cntnap2_mPFC_bRPLC_F02.mzXML	Mzxml

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Publications

Cntnap2-dependent molecular networks in autism spectrum disorder revealed through an integrative multi-omics analysis.

Jang Wooyoung Eric WE Park Ji Hwan JH Park Gaeun G Bang Geul G Na Chan Hyun CH Kim Jin Young JY Kim Kwang-Youl KY Kim Kwang Pyo KP Shin Chan Young CY An Joon-Yong JY Lee Yong-Seok YS Kim Min-Sik MS

Molecular psychiatry 20221017 2

Autism spectrum disorder (ASD) is a major neurodevelopmental disorder in which patients present with core symptoms of social communication impairment, restricted interest, and repetitive behaviors. Although various studies have been performed to identify ASD-related mechanisms, ASD pathology is still poorly understood. CNTNAP2 genetic variants have been found that represent ASD genetic risk factors, and disruption of Cntnap2 expression has been associated with ASD phenotypes in mice. In this stu ...[more]

PMID: 36253443

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