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공공누리This item is licensed Korea Open Government License

Title
Transcriptome analyses suggest minimal effects of Shank3 dosage on directional gene expression changes in the mouse striatum
Author(s)
강효진한기훈이연금장인화김윤희진춘매
Publisher
Korean Society for Integrative Biology
Publication Year
2019-04-12
Abstract
Both deletions and duplications of the SH3 and multiple ankyrin repeat domains 3 (SHANK3) gene, encoding excitatory postsynaptic scaffolds, are causally associated with various brain disorders, suggesting that proper Shank3 dosage is critical for normal brain development and function. In addition to its well-established synaptic functions, recent studies have suggested that Shank3 can also affect gene expression in the nucleus. However, it has not been investigated whether there are a group of genes whose directional expression is regulated in a Shank3 dosage-dependent manner (i.e. showing opposite changes in expression following Shank3 reduction and overexpression). This is an important issue to be examined for better understanding why neuronal development and function are sensitive to Shank3 dosage, and how much transcriptional changes contribute to neuronal phenotypes affected by Shank3 dosage. To examine this, we performed transcriptome analyses on the striatum of Shank3 heterozygous and knock-out mice, which identified three and 17 differentially expressed genes, respectively. We then compared the results to those of our previous striatal transcriptome analysis of Shank3 overexpressing mice and identified 31 candidate genes showing directional expression changes in a Shank3 dosage-dependent manner. However, overall, their Shank3 dosage-dependent fold changes were very subtle (average of absolute log2(fold change) was 0.139). Meanwhile, the gene set enrichment analyses of the striatal transcriptome suggested that Shank3 dosage may affect anchoring junction-related functions. Taken together, these results suggest that Shank3 dosage minimally affects directional gene expression changes in the mouse striatum.
Keyword
Shank3 dosage; striatum; transcriptome
Journal Title
Animal Cells and Systems;
Citation Volume
23
ISSN
1976-8354
DOI
10.1080/19768354.2019.1595142
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Appears in Collections:
7. KISTI 연구성과 > 학술지 발표논문
URI
https://repository.kisti.re.kr/handle/10580/16046
Fulltext
 https://scienceon.kisti.re.kr/srch/selectPORSrchArticle.do?cn=NART103236699
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