We acknowledge funding National Institute of Mental Health (NIMH) R01 MH113948 (to CMP), Civitan International Research Center Emerging Scholar Award (to QQX) and Core grant from National Cancer Institute (P30 CA013148) through the O’Neal Comprehensive Cancer Center (to JAM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Proteins -- Metabolism, Proteomics, Molecular biology, Mitosis
Autism Spectrum Disorder (ASD) is a developmental disorder in which children display repetitive behavior, restricted range of interests, and atypical social interaction and communication. CUL3, coding for a Cullin family scaffold protein mediating assembly of ubiquitin ligase complexes through BTB domain substrate-recruiting adaptors, has been identified as a high-risk gene for autism. Although complete knockout of Cul3 results in embryonic lethality, Cul3 heterozygous mice have reduced CUL3 protein, demonstrate comparable body weight, and display minimal behavioral differences including decreased spatial object recognition memory. In measures of reciprocal social interaction, Cul3 heterozygous mice behaved similarly to their wild-type littermates. In area CA1 of hippocampus, reduction of Cul3 significantly increased mEPSC frequency but not amplitude nor baseline evoked synaptic transmission or paired-pulse ratio. Sholl and spine analysis data suggest there is a small yet significant difference in CA1 pyramidal neuron dendritic branching and stubby spine density. Unbiased proteomic analysis of Cul3 heterozygous brain tissue revealed dysregulation of various cytoskeletal organization proteins, among others. Overall, our results suggest that Cul3 heterozygous deletion impairs spatial object recognition memory, alters cytoskeletal organization proteins, but does not cause major hippocampal neuronal morphology, functional, or behavioral abnormalities in adult global Cul3 heterozygous mice.
Copyright (c) 2023 The Authors
This work is licensed under a Creative Commons Attribution 4.0 International License.
Locate the Document
Xia, Q. Q., Walker, A. K., Song, C., Wang, J., Singh, A., Mobley, J. A., ... & Powell, C. M. (2023). Effects of heterozygous deletion of autism-related gene Cullin-3 in mice. Plos one, 18(7), e0283299.