Education, Research, Patient Care qd

Zebrafish knockout of Down syndrome gene, DYRK1A, shows social impairments relevant to autism

September 29, 2017

Authors: Kim OH, Cho HJ, Han E, Hong TI, Ariyasiri K, Choi JH, Hwang KS, Jeong YM, Yang SY, Yu K, Park DS, Oh HW, Davis EE, Schwartz CE, Lee JS, Kim HG, Kim CH.

Abstract: DYRK1A maps to the Down syndrome critical region at 21q22. Mutations in this kinase-encoding gene have been reported to cause microcephaly associated with either intellectual disability or autism in humans. Intellectual disability accompanied by microcephaly was recapitulated in a murine model by overexpressing Dyrk1a which mimicked Down syndrome phenotypes. However, given embryonic lethality in homozygous knockout (KO) mice, no murine model studies could present sufficient evidence to link Dyrk1a dysfunction with autism. To understand the molecular mechanisms underlying microcephaly and autism spectrum disorders (ASD), we established an in vivo dyrk1aa KO model using zebrafish. In this study, we established a zebrafish model to validate a candidate gene for autism in a vertebrate animal. These results illustrate the functional deficiency of DYRK1A as an underlying disease mechanism for autism. We also propose simple social behavioral assays as a tool for the broader study of autism candidate genes.

Source

PubMed ID

29021890