| Model Type | Specific Model Name | Species | Genes Involved | OCD-like Phenotypes Observed | Brain Regions/Circuits Affected | Utility/Applications | Limitations |
|---|---|---|---|---|---|---|---|
| Genetic knockout | Hoxb8-KO | Mouse | **Hoxb8** | Excessive grooming/self-injury–like repetitive behavior; compulsive grooming phenotype used as an OCD-relevant endophenotype | Cortico-striato-thalamo-cortical (CSTC)-relevant circuitry broadly implicated; also linked to microglial/hematopoietic contributions rather than a single canonical OCD node (pqac-00000007) | Useful for studying repetitive grooming, neuroimmune contributions, and disentangling compulsive motor output from anxiety-like behaviors (pqac-00000007) | Face validity for grooming is strong, but limited construct validity for intrusive obsessions; captures only a subset of human OCD phenomenology (pqac-00000007) |
| Genetic knockout | Slc1a1-KO | Mouse | **Slc1a1** / EAAT3 | Repetitive/compulsive-like behaviors and anxiety-related phenotypes in an OCD risk-gene framework | Glutamatergic signaling within CSTC-related circuits; striatum/cortex glutamate homeostasis is the main mechanistic relevance (pqac-00000007, pqac-00000008) | Useful for probing glutamatergic mechanisms and testing candidate glutamate-modulating interventions (pqac-00000007, pqac-00000008) | Human OCD is polygenic; single-gene knockout incompletely models symptom heterogeneity and cognitive obsessions (pqac-00000007) |
| Genetic knockout | Sapap3-KO | Mouse | **Sapap3 / Dlgap3** | Excessive grooming, anxiety-like behavior, repetitive acts; one of the best-established compulsive grooming models | Corticostriatal synapses, especially striatal dysfunction within CSTC circuitry (pqac-00000007, pqac-00000008) | High translational value for corticostriatal synaptopathy, habit/compulsivity mechanisms, and rescue experiments with circuit or pharmacologic interventions (pqac-00000007) | Strong for compulsions/grooming but does not model intrusive obsessions or full symptom dimensions seen in humans (pqac-00000007, pqac-00000008) |
| Genetic knockout | Slitrk5-KO | Mouse | **Slitrk5** | Excessive grooming and anxiety-like/compulsive-like behaviors | Orbitofrontal-striatal and broader CSTC dysfunction relevant to compulsivity (pqac-00000007, pqac-00000008) | Useful for studying synaptogenesis-related mechanisms and corticostriatal abnormalities in OCD-like behavior (pqac-00000007) | Limited to a narrow behavioral phenotype; genetic effect sizes in humans are smaller and more polygenic than in knockout models (pqac-00000007) |
| Genetic knockout | Spred2-KO | Mouse | **Spred2** | Repetitive grooming/compulsive-like behavior in transgenic OCD modeling summaries | CSTC-related signaling abnormalities; mechanistically linked to intracellular signaling regulation rather than a single OCD-specific node (pqac-00000007) | Useful for investigating intracellular signaling contributions to repetitive behavior and for comparative model selection across transgenic strains (pqac-00000007) | Less extensively validated than Sapap3-KO; uncertain breadth of translational relevance to diverse OCD symptom dimensions (pqac-00000007) |
| Genetic/optogenetic circuit model | Repeated OFC–VMS stimulation model | Mouse | Circuit perturbation model rather than a single gene | Induced OCD-like grooming/compulsive behavior after repeated stimulation | **Orbitofrontal cortex (OFC)** and **ventromedial striatum (VMS)** within CSTC loops (pqac-00000008) | Strong causal tool for testing whether abnormal CSTC activity can generate compulsive behaviors; valuable for circuit-level intervention studies (pqac-00000008) | Not a natural disease model; limited ecological validity and does not capture developmental/polygenic aspects of OCD (pqac-00000008) |
| Transgenic model class | Knockout mouse models (aggregate class reviewed in recent literature) | Mouse | Includes **Hoxb8, Slc1a1, Sapap3, Slitrk5, Spred2** | Repetitive grooming, anxiety-like behavior, compulsive-like rituals; model-specific variation | Recurrently implicate **CSTC circuits**, especially orbitofrontal, striatal, and thalamic pathway abnormalities (pqac-00000007, pqac-00000008) | Comparative platform for selecting models by mechanism: synaptic, glutamatergic, signaling, or neuroimmune hypotheses; supports neuromodulation and drug development work (pqac-00000007) | No single model captures the full human syndrome, especially obsessions, symptom dimensions, fluctuating insight, and comorbidity (pqac-00000007, pqac-00000008) |
| Zebrafish genetic model | **slitrk5a** altered zebrafish model | Zebrafish | **slitrk5a** | “Checking”-like repetitive behavior reported as OCD-like in zebrafish model literature | Vertebrate brain circuit analogs relevant to repetitive behavioral control; not directly homologous to mammalian CSTC architecture (pqac-00000007) | Useful for high-throughput genetics and drug screening, rapid developmental studies, and comparative validation of OCD risk genes (pqac-00000007) | Behavioral homology to human obsessions/compulsions is indirect; circuit correspondence to human OCD is limited (pqac-00000007) |
| Other species/model note | Zebrafish and other lower-animal OCD-relevant models (general mention) | Zebrafish / lower vertebrates | Varies by construct | Repetitive/compulsive-like phenotypes are used as analog readouts | Developmental and conserved neural pathway studies; not direct one-to-one CSTC replication (pqac-00000007) | Helpful for scalable screening and testing conserved gene-function effects across species (pqac-00000007) | Reduced face validity for complex human psychopathology, especially intrusive thoughts and higher-order cognition (pqac-00000007) |
| Pharmacological / environmental models | Not specified in the available OCD contexts | Not specified | Not specified | Typically used in the field for repetitive behavior provocation, but no specific OCD pharmacological model was detailed in the available contexts | Not specified in available contexts | Can complement genetic models when available | Not enough source detail in the available contexts to summarize specific models responsibly (pqac-00000007) |


*Table: This table summarizes major animal models used in obsessive-compulsive disorder research, emphasizing transgenic mouse lines and zebrafish models mentioned in the available sources. It is useful for comparing each model’s phenotypes, implicated circuits, translational uses, and major limitations.*