The 22q11 mouse model (Df(h22q11)/+) is primarily used to study human 22q11.2 deletion syndrome (also known as DiGeorge syndrome and/or velocardiofacial syndrome), enabling investigation of the underlying neurodevelopmental pathophysiological processes, as well as preclinical efficacy studies evaluating novel therapeutics targeting cognitive and/or behavioral deficits associated with the 22q11.2 microdeletion. In humans, 22q11.2 microdeletions typically range from 3Mb (approx., 60 genes) to 1.5 Mb (approx., 35 genes), known genes that are predominantly expressed in the brain, with examples including DGCR6, PRODH, RANBP1, DGCR8, COMT, TBX1, and HIRA (Maynard et al., 2003).  

As described in the original publication (Diederiksen et al., 2017), the mouse model recapitulates the orthologous region of mouse chromosome 16 (MMU 16qA13) corresponding to the human 22q11.2 locus, demonstrating strong construct validity between the model and human 22q11.2 deletion carriers. The Df((h22q11)/+) line carries a 1.13Mb microdeletion spanning Dgcr2-Hira, encompassing orthologs of all functional genes in the critical human 22q11.2 region with except CLTCL, and Igl1 which is not part of human region and has not previously been linked to behavior or cognition in the mouse (Didriksen et al., 2017; Nilsson et al., 2016). 

Several genes within the deleted region also contribute to psychiatric vulnerability, making the 22q11 mouse model a relevant platform for studying schizophrenia-relevant phenotypes. Notably, COMT, PRODH, TBX1, and ZDHHC8 are among the most studied schizophrenia risk genes, affecting dopamine signaling, excitatory/inhibitory balance, synaptic stability, and cognitive function. Therefore, the 22q11 mouse model is also suitable to investigate the preclinical efficacy of novel therapeutics targeting schizophrenia-related deficits, such as impairments in sensorimotor gating.  

Because the deletion affects multiple conserved genes and pathways, individuals with 22q11.2 deletion syndrome can present with a broad spectrum of phenotypes, including developmental delay, speech and language impairment, intellectual disability, seizures, autism spectrum features, attention deficits, hyperactivity, and behavioral dysregulation, as well as physical manifestations such as facial dysmorphisms, short stature, and hypotonia. Consequently, the 22q11 mouse model may also be applied to study broader neurodevelopmental and psychiatric phenotypes associated with these genes and to evaluate therapeutics targeting downstream circuits, pathways, or specific symptom domains.  

22q11マウスモデルが、22q11.2欠失症候群、統合失調症、および関連する神経発達障害や精神疾患に対する治療候補薬の開発をどのように促進できるか、当社の専門家にご相談ください。