Neuroscience mouse models enable researchers to investigate the molecular and cellular mechanisms underlying brain function and dysfunction. From cell type specific knockouts that dissect neural circuit function to disease mutation knockins that model neurological conditions, the right model design is critical for understanding the nervous system and developing treatments for neurological disorders.
Conditional approaches are particularly important in neuroscience, where the same gene often has distinct functions in different neuronal populations, glial cells, and developmental stages. ingenious targeting laboratory designs and generates custom neuroscience models tailored to your specific research questions.
Cell Type Specific Approaches
Neuronal Cre Drivers
Conditional knockouts enable gene deletion in specific neuronal populations:
| Cre Driver | Target Population | Timing | Applications |
|---|---|---|---|
| Nestin Cre | Neural progenitors | E10.5 | Pan neural knockout |
| Synapsin Cre | Mature neurons | Postnatal | Post mitotic neuron function |
| CamKIIα Cre | Forebrain excitatory neurons | P14+ | Learning, memory, cognition |
| Emx1 Cre | Cortical excitatory neurons | E10.5 | Cortical development, function |
| DAT Cre | Dopaminergic neurons | E15 | Reward, movement, Parkinson |
| Chat Cre | Cholinergic neurons | E12.5 | Motor function, cognition |
| Pvalb Cre | Parvalbumin interneurons | Postnatal | Inhibitory circuits, oscillations |
| Sst Cre | Somatostatin interneurons | Postnatal | Cortical inhibition |
| Vgat Cre | GABAergic neurons | E12.5 | All inhibitory neurons |
| Vglut2 Cre | Glutamatergic neurons | E11.5 | Excitatory transmission |
Glial Cre Drivers
| Cre Driver | Target Population | Timing | Applications |
|---|---|---|---|
| GFAP Cre | Astrocytes | E14.5 | Glial function, gliosis |
| Aldh1l1 Cre | Astrocytes | Postnatal | More specific astrocyte targeting |
| Olig2 Cre | Oligodendrocyte lineage | E12.5 | Myelination |
| PLP Cre | Mature oligodendrocytes | Postnatal | Myelin maintenance |
| CX3CR1 Cre | Microglia | Embryonic | Neuroinflammation |
Inducible Neural Cre Lines
Tamoxifen inducible Cre (CreERT2) enables temporal control over gene deletion in the nervous system:
Inducible systems enable adult onset gene deletion, bypassing developmental requirements and modeling acute loss of function.
Neurodegenerative Disease Models
Alzheimer Disease
Models addressing amyloid and tau pathology:
- APP knockin models expressing familial AD mutations
- Tau knockin and humanization models
- Presenilin knockout and knockin models
- Microglial gene modifications for neuroinflammation studies
Parkinson Disease
Models for dopaminergic neuron biology and alpha synuclein pathology:
- Alpha synuclein knockin and overexpression models
- LRRK2 mutation knockins
- PINK1, Parkin, DJ1 knockouts for mitochondrial dysfunction
- DAT Cre mediated conditional knockouts in dopaminergic neurons
ALS and Motor Neuron Disease
Models for motor neuron degeneration:
- SOD1 mutation knockins (G93A, G85R)
- TDP43 and FUS mutation models
- C9orf72 repeat expansion models
Huntington Disease
Models for polyglutamine expansion pathology:
- HTT knockin models with expanded CAG repeats
- Conditional HTT knockouts
- Striatal specific models using D1R or D2R Cre drivers
Research Applications
Neural Circuit Dissection
Cell type specific knockouts enable circuit level analysis:
- Identify which neurons require specific genes for circuit function
- Distinguish cell autonomous from circuit level effects
- Map gene function to specific neural populations
- Combine with optogenetics and chemogenetics
Synaptic Function
Models for studying synaptic transmission and plasticity:
- Receptor knockout and knockin models
- Synaptic vesicle and release machinery modifications
- Postsynaptic density protein studies
- Synaptic plasticity gene modifications
Behavioral Studies
Models supporting behavioral neuroscience:
- Learning and memory (hippocampal, cortical)
- Anxiety and depression (limbic circuits)
- Motor function (basal ganglia, cerebellum)
- Social behavior (prefrontal, amygdala)
- Reward and addiction (VTA, nucleus accumbens)
Developmental Neuroscience
Models for neural development studies:
- Neural progenitor gene function
- Neuronal migration and differentiation
- Axon guidance and synaptogenesis
- Critical period plasticity
Model Types for Neuroscience
Conditional Knockout
Essential for neuroscience due to:
- Many neural genes cause embryonic lethality when deleted globally
- Cell type specificity reveals circuit level gene function
- Temporal control distinguishes developmental from adult roles
- Brain region specificity possible with appropriate Cre drivers
Point Mutation Knockin
Model disease associated variants at physiological levels:
- Familial disease mutations (AD, PD, HD)
- GWAS identified risk variants
- Phosphorylation site mutations for signaling studies
Reporter Knockin
Visualize gene expression and cell populations:
- Cell type markers for identification and sorting
- Activity reporters for functional imaging
- Lineage tracing of neural progenitors
Technical Considerations
Strain Background
Strain background affects neural and behavioral phenotypes:
C57BL/6 is generally preferred for neuroscience to enable comparison with published literature and behavioral databases.
Behavioral Phenotyping Considerations
- Age matching for behavioral cohorts
- Sex as biological variable
- Circadian timing of testing
- Environmental standardization
- Appropriate statistical power
Selected Publications
Neuroscience models generated by ingenious targeting laboratory:
Vacher CM et al. (2021).
Placental endocrine function shapes cerebellar development and social behavior. ↗Nature Neuroscience 24(10): 1392-1401
Chakrabarti S et al. (2024).
Touch sensation requires the mechanically gated ion channel ELKIN1. ↗Science 383(6686): 992-998
Clausen BE et al. (1999).
Conditional gene targeting in macrophages and granulocytes using LysMcre mice. ↗Transgenic Research 8(4): 265-277
What Researchers Say
“ingenious Targeting Laboratory is highly recommended for generating custom animal models. Past 2 years, we have made 2 conditional knockout mouse lines. All processes of each project were scientifically and professionally handled. Their scientific consulting to initiate the project was superb compared to other companies, and transparency of the project progress reported by project managers was excellent. Their excellency and dedication to meet our needs in a timely manner are invaluable to continuation of our research progress.”
— Hyekyung Plumley, PhD
Warren Center for Neuroscience Drug Discovery
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