Powering Breakthroughs in Preclinical Autism Spectrum Disorder (ASD) Studies

Approximately 2% of individuals with autism carry detrimental mutations in the SHANK3 gene, which plays a crucial role in organizing neuronal connections. ASD is a multifaceted neurodevelopmental condition characterized by challenges in social interaction, communication, and behavior. At PsychoGenics, we offer a well-validated Shank3B-KO mouse model.

The Shank3B-KO Mouse Model

About 2% of people with autism carry harmful mutations in SHANK3, a protein that helps organize the connections between neurons​ Developed by Guoping Feng, Shank3 –Feng mice harbor a deletion of exons 13-16 of the PDZ domains leading to the deletion of the Shank3α and Shank3β isoforms and partial deletion of Shank3γ​. These mice exhibit some social, communicative, repetitive, and sensory processing abnormalities associated with autism spectrum disorder, as well as:

  • Social deficits
  • Decreased activity and locomotion
  • Altered gait patterns
  • Anxiety-like behaviors
  • Modified startle responses and increased pre-pulse inhibition

Results have been replicated across studies.

Electrophysiology & Disease Markers

(A) Synaptically driven extracellular field potentials and (B) whole-cell currents from medium spiny neurons evoked in dorsolateral striatum by stimulating corpus callosum – major cortical input into basal ganglia – were significantly smaller in Shank3/F KO mice. (C) Synaptically driven extracellular field potentials in nucleus accumbens evoked by stimulation within nucleus accumbens were also significantly reduced in KO mice.
Developed by Guoping Feng. These mice are KO for Shank3α, Shank3β isoforms and are partial KO for Shank3γ isoform.

Quantitative PCR (qPCR) analysis of striatal and cortical tissues from shank 3 ko males at 15-17 wks of age. Relative level of target genes (psd95, syp, glur1, glur2, nr2a, nr2b, bdnf isoforms I, IV, VI, IX) were:

First normalized to the housekeeping gene gapdh and then normalized to the tissue-matched WT cohorts.