Effects of heterozygous deletion of autism-related gene Cullin-3 in mice

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 d...

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Bibliographic Details
Published in:PloS one 2023-07, Vol.18 (7), p.e0283299-e0283299
Main Authors: Xia, Qiang-Qiang, Walker, Angela K, Song, Chenghui, Wang, Jing, Singh, Anju, Mobley, James A, Xuan, Zhong X, Singer, Jeffrey D, Powell, Craig M
Format: Article
Language:English
Subjects:
Abnormalities
Analysis
Animals
Antibodies
Autism
Autism Spectrum Disorder - genetics
Autistic Disorder - genetics
Biology and Life Sciences
Body weight
Care and treatment
Chromosome deletion
Coding
Copy number variations
Cullin
Cullin Proteins - genetics
Cullin Proteins - metabolism
Cytoskeleton
Deletion
Dendritic branching
Dendritic spines
Developmental disabilities
Diagnosis
Gene deletion
Genes
Genetic aspects
Health aspects
Hippocampus
Interpersonal relations
Laboratory animals
Lethality
Ligases
Medicine and Health Sciences
Membranes
Mice
Morphology
Mutation
Neomycin
Neural coding
Neurons
Object recognition
Pattern recognition
Protein Binding
Proteins
Proteomics
Research and Analysis Methods
Scientific equipment and supplies industry
Social aspects
Social behavior
Social factors
Social Sciences
Spatial memory
Spine
Substrates
Synaptic transmission
Ubiquitin
Ubiquitin-protein ligase
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0283299