Altered synaptic ultrastructure in the prefrontal cortex of Shank3-deficient rats.
Sarah Jacot-Descombes, Neha U Keshav, Dara L Dickstein and 10 others
PMID 33203459WHAT IT FOUND
Rats with one mutated Shank3 gene showed larger synapse heads in the prefrontal cortex, while those with two mutated copies did not.
This suggests haploinsufficiency may drive specific structural changes relevant to autism and Phelan-McDermid syndrome.
Key findings
01Heterozygous rats had significantly larger spine head diameters and postsynaptic densities compared to wild-type and homozygous knockout rats.
02Homozygous knockout rats showed no significant differences in synaptic ultrastructure compared to wild-type rats.
03Basal dendritic length and overall spine density were comparable across all three genotypes.
STILL TO COME
How it was doneWhat they found
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What it does not show
This is an animal study using rats, so the findings may not directly translate to human patients. The electron microscopy part of the study used only male rats, so it is unclear if the same synaptic changes occur in females. The genetic mutation in the rats affects only part of the protein (the ANK domain), which may not fully mimic all human SHANK3 mutations that delete the entire gene. The study only looked at rats at 5 weeks of age, so it does not show how these structures might change as the animals mature.
Declared interests
The study was funded by the Beatrice and Samuel A. Seaver Foundation, Simons Foundation, Foundation for Prader-Willi Research, and the Foundation for the National Institutes of Health.
The easy way to misread this
Do not assume that having two mutated copies of the Shank3 gene causes more severe structural damage than having one. In this study, the rats with only one mutated copy showed the significant synaptic enlargement, while those with no functional copies looked similar to normal controls.