P2.136 Thursday, Jan. 5 Knockdown of putative Autism genes, SYNGAP and SHANK3, in zebrafish disrupts rhythmic motor behaviors. KOZOL, RA*; DALLMAN, JE; PERICAK-VANCE, MA; University of Miami email@example.com
A robust and stereotypic behavioral repertoire makes zebrafish a suitable model to understand the functional link between genes and behavior. Our goal is to establish an Autism Spectrum Disorders (ASD) zebrafish model to study the mechanistic underpinnings of implicated genes that are conserved in zebrafish. As a first step we are knocking down putative human autism genes and characterizing the resultant behaviors in zebrafish. To knockdown gene expression we use morpholino anti-sense technology. Morpholinos were designed against SHANK3 and SYNGAP, two ASD implicated genes with important roles in the postsynaptic density (PSD) of the glutamatergic synapse. Morpholinos were shown to disrupt normal splicing, producing either exon-skipping or intronic insertions and resulting in protein truncations. Morpholino injected zebrafish display disrupted behaviors. Morphant behavior progresses from uncoordinated coiling/bending at embryonic stages to unproductive swims (“wobble”) at later stages. Our hypothesis is that the “wobble” phenotype results from tonic excitation that reduces the ability of the fish to produce strong alternating bends seen in control larvae. These studies in zebrafish represent one branch of a multidisciplinary collaboration to achieve a better understanding of Autism Spectrum Disorders.