Identification of two novel Shank3 transcripts in the developing mouse neocortex
Article first published online: 14 NOV 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 128, Issue 2, pages 280–293, January 2014
How to Cite
J. Neurochem. (2014) 128, 280–293.
- Issue published online: 6 JAN 2014
- Article first published online: 14 NOV 2013
- Accepted manuscript online: 24 OCT 2013 11:26AM EST
- Manuscript Accepted: 18 OCT 2013
- Manuscript Revised: 2 OCT 2013
- Manuscript Received: 14 MAY 2013
- Ministry of Health, Labour and Welfare of Japan
- Ministry of Education, Culture, Sports, and Science and Technology of Japan
- Japan Foundation for Pediatric Research
- autism spectrum disorder;
- DNA methylation;
SHANK3 is a synaptic scaffolding protein enriched in the post-synaptic density of excitatory synapses. Since several SHANK3 mutations have been identified in a particular phenotypic group of patients with autism spectrum disorder (ASD), SHANK3 is strongly suspected of being involved in the pathogenesis and neuropathology of ASD. Several SHANK3 isoforms are known to be produced in the developing brain, but they have not been fully investigated. Here, we identified two different amino-terminus truncated Shank3 transcripts. One transcript, designated as Shank3c-3, produces an isoform that contains the entire carboxyl-terminus, but the other transcript, designated as Shank3c-4, produces a carboxyl-terminus truncated isoform. During development, expression of the novel Shank3 transcripts increased after birth, transiently decreased at P14 and then gradually increased again thereafter. We also determined that methyl CpG-binding protein 2 (MeCP2) is involved in regulating expression of the novel Shank3 transcripts. MeCP2 is a transcriptional regulator that has been identified as the causative molecule of Rett syndrome, a neurodevelopmental disorder that includes autistic behavior. We demonstrated a difference between the expression of the novel Shank3 transcripts in wild-type mice and Mecp2-deficient mice. These findings suggest that the SHANK3 isoforms may be implicated in the synaptic abnormality in Rett syndrome.
SHANK3 is a synaptic scaffolding protein and is suspected of being implicated in the pathogenesis and neuropathology of ASD. We here identified two different amino-terminus truncated Shank3 transcripts, Shank3c-3 and Shank3c-4, expressed from the intron 10 of the Shank3 gene, and also suggested the epigenetic regulation of their expression via methyl CpG-binding protein 2 (MeCP2) that has been identified as the causative molecule of Rett syndrome.