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.
Shank3 KO mice weigh more than their WT counterparts.
Shank3 KO mice show significantly more grooming behavior and for longer bouts.
Shank3 KO show deficits in startle response.
Male Shank3 KO mice show decreased locomotor and rearing activities when presented with urine of an estrus female mouse.
- Male KO mice are placed in an open field where they are presented with the urine of an estrus female placed in the center of the open field chamber.
- Locomotor activity is recorded automatically to determine social function
Rotarod Performance: Male Shank3 KO mice show some impairment on rotarod performance. They fall quicker from the rotating rod and at slower speeds.
Male Shank3 KO show less social interaction compared to WT mice.
- Same-genotype and age dyads are allowed to freely interact for 10 minutes
- Number of interactions (body contacts) are measured
Electrophysiology & Disease Markers
Clinical evidence supports involvement of striatal circuits in autism spectrum disorders (ASD) pathophysiology. Shank family proteins are an integral part of postsynaptic density in excitatory synapses. Shank3 is enriched in striatum and its mutations have been linked to both ASD and schizophrenia. Shank3/F mutant mice developed by Guoping Feng3 show behavioral abnormalities associated with ASD.
Synaptic Transmission in Striatum and NAc:
(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.
Cortical BDNF Isoforms and Striatal Synaptic Plasticity Marker mRNA Expression in 15-17 Weeks-Old Shank3 Mutant 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.
Partnering to Optimize Your Preclinical ASD Research
Through behavioral assessments and comprehensive analysis, PsychoGenics enables vital insights into the molecular and behavioral aspects of autism spectrum disorder. Collaborate with us to push the boundaries of preclinical ASD research and accelerate your progress.
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