Identification of a novel Shank2 transcriptional variant in Shank2 knockout mouse model of autism spectrum disorder

Yong Seok Lee, Nam Kyung Yu, Jeewan Chun, Jung Eun Yang, Chae Seok Lim, Hyopil Kim, Gaeun Park, Jin A. Lee, Kyungmin Lee, Bong Kiun Kaang, Jae Hyung Lee

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that are highly heterogeneous in clinical symptoms as well as etiologies. Mutations in SHANK2 are associated with ASD and accordingly, Shank2 knockout mouse shows ASD-like behavioral phenotypes, including social deficits. Intriguingly, two lines of Shank2 knockout (KO) mouse generated by deleting different exons (exon 6-7 or exon 7) showed distinct cellular phenotypes. Previously, we compared gene expressions between Shank2 KOs lacking exon 6-7 (e6-7 KO) and KOs lacking exon 7 (e7 KO) by performing RNA-seq. In this study, we expanded transcriptomic analyses to identify novel transcriptional variants in the KO mice. We found prominent expression of a novel exon (exon 4′ or e4') between the existing exons 4 and 5 in the Shank2 e6-7 KO model. Expression of the transcriptional variant harboring this novel exon was confirmed by RT-PCR and western blotting. These findings suggest that the novel variant may function as a modifier gene, which contributes to the differences between the two Shank2 mutant lines. Furthermore, our result further represents an example of genetic compensation that may lead to phenotypic heterogeneity among ASD patients with mutations in the same gene.

Original languageEnglish
Article number54
JournalMolecular brain
Issue number1
StatePublished - 6 Apr 2020


  • Autism spectrum disorder
  • RNA-seq
  • Shank2


Dive into the research topics of 'Identification of a novel Shank2 transcriptional variant in Shank2 knockout mouse model of autism spectrum disorder'. Together they form a unique fingerprint.

Cite this