In contrast to many earlier models that retain partial SHANK3 isoform expression due to limited exon targeting, the Shank3 Ex4-22 del mouse model is uniquely engineered with deletions of exons 4 through 22, preventing the expression of all major murine SHANK3 protein isoforms, making it more representative on the genetic level of the large deletions that are typically found in Phelan-McDermid Syndrome patients. For gene therapies or antisense oligonucleotide (ASO) strategies aiming to restore SHANK3 function, the presence of residual SHANK3 protein isoforms can complicate interpretation of treatment effects.  

Therefore, the Ex4–22-del model represents a more genetically accurate mouse model, well-suited for testing gene therapies and ASOs targeting SHANK3 haploinsufficiency. This model was previously independently developed by two groups and first described in literature by Wang et al., 2016 and Drapeau et al., 2018, providing foundational insights into its construct validity and translational relevance. Moreover, the Ex4-22 del mice are bred on a C57BL/6 background, which is a widely used and well-characterized mouse strain that supports reproducible behavioural and physiological studies.  

The Shank3 Ex4–22-del mouse model is relevant for researchers working at the intersection of synaptopathies, haploinsufficiency disorders, and neurodevelopmental diseases. It is particularly relevant to preclinical programs in: 

• Phelan-McDermid Syndrome (PMS) – where SHANK3 haploinsufficiency is a known driver of the disease pathophysiology  

• Autism Spectrum Disorder (ASD) – especially genetically defined subtypes like SHANK3-related ASD 

• Intellectual Disability – often co-occurring with SHANK3 mutations 

Explore how this license-free model can accelerate your program. Contact CureSHANK to access the model for in-house studies or connect with InnoSer for preclinical service availability starting in 2026.