Intestinal dysmotility in a zebrafish (Danio rerio) shank3a;shank3b mutant model of autism.
David M James, Robert A Kozol, Yuji Kajiwara and 6 others
PMID 30733854WHAT IT FOUND
Zebrafish larvae with mutations in SHANK3-related genes had slower gut movement than normal larvae.
Their intestinal contractions were less frequent, and fluorescent beads took longer to pass through the gut. The work does not show an effect in people.
Key findings
01Zebrafish larvae with the shank3abΔC +/− genotype had less frequent intestinal peristaltic contractions than wild-type larvae.
02After feeding fluorescent beads, shank3abΔC +/− larvae took longer than 12 hours to begin passing beads, and some had not passed all beads by 24 hours.
03In mutant zebrafish larvae, injecting the longest human SHANK3 mRNA partially improved transit from the intestinal bulb to the upper intestine, but lower-intestine transit was not rescued.
STILL TO COME
How it was doneWhat they found
Read the rest of this summary
You get three full summaries a month, free, and we do not ask for a card. Search, the TL;DRs and your library stay unlimited either way.
What it does not show
The study was done in zebrafish larvae and adult fish, not in people with autism or Phelan-McDermid syndrome. It did not test a physical therapy, occupational therapy, or speech-language therapy intervention. The bead transit assay did not test appetite or jaw shape, which could affect feeding and bead intake. Human SHANK3 mRNA rescue was only partial and did not fix lower-intestine transit. The injected mRNA is expressed transiently for about 48 hours, so it may not model later gut development. The authors say a causal link between fewer enteroendocrine cells and reduced gut movement needs future experiments.
Declared interests
The supplied text lists funding from the National Institutes of Health, Florida Education Fund, Howard Hughes Medical Institute, the Beatrice and Samuel A. Seaver Foundation, and the National Institute of Child Health and Human Development. It does not include a statement of author competing interests.
The easy way to misread this
Do not read this as evidence that a treatment can improve gut motility in people with autism. The study reports gut movement findings in zebrafish larvae, and the only rescue was injection of human SHANK3 mRNA into fish embryos.