CRMP1 Mouse

What is CRMP1 and why is it significant in neuroscience research?

CRMP1 belongs to the collapsin response mediator protein family that plays crucial roles in brain development and function. It is involved in various aspects of neuronal development including axonal guidance, neuronal migration, and neurite outgrowth . The significance of CRMP1 in neuroscience research has grown substantially as recent studies have linked CRMP1 gene variants to neurodevelopmental disorders in humans, including intellectual disability and autism spectrum disorder . Additionally, CRMP1-deficient mice exhibit behavioral abnormalities that model aspects of schizophrenia, making this protein a valuable target for studying neuropsychiatric conditions .

What are the major phenotypes observed in CRMP1-deficient mice?

CRMP1-deficient mice (crmp1−/−) display several distinctive phenotypes:

Behavioral phenotypes:

• Hyperactivity in both light and dark phases of activity cycles

• Impaired emotional behavior in elevated plus maze and forced swim tests

• Decreased prepulse inhibition (rescuable by antipsychotic drugs)

• Impaired context-dependent memory and long-term memory retention

Neurobiological phenotypes:

• Enhanced methamphetamine-induced dopamine release in prefrontal cortex

• Reduced long-term potentiation (LTP) in the CA1 region of hippocampus

• Altered dendritic organization with intense MAP2 staining in proximal dendrites but reduced and disorganized staining in distal dendrites

• Decreased GAP-43 and PSD95 immunoreactivity in the CA1 region

This combination of phenotypes makes CRMP1 knockout mice particularly valuable for modeling aspects of schizophrenia and other neurodevelopmental disorders.

What role does CRMP1 play in normal neuronal development?

CRMP1 has several critical functions in neuronal development:

• Neurite outgrowth: CRMP1 is essential for proper neurite outgrowth in the hippocampus and other brain regions . In CRMP1-deficient mice, there are alterations in MAP2 staining patterns, indicating disrupted dendritic organization.

• Synaptic plasticity: CRMP1 contributes to long-term potentiation, particularly in the maintenance phase, which is crucial for learning and memory formation .

• Dendritic development: CRMP1 is involved in dendritic organization and spine maturation of cortical and hippocampal neurons .

• Cerebellar development: Loss of CRMP1 during development leads to reduced granule cell proliferation, increased apoptosis, and migration defects in the cerebellum .

The function of CRMP1 is regulated by phosphorylation through kinases such as Cdk5, Rho/ROCK, and GSK3, which control its activity in a spatiotemporal manner during development .

How should researchers design behavioral testing protocols for CRMP1 mouse models?

When designing behavioral testing protocols for CRMP1 mouse models, researchers should consider several important methodological aspects:

• Test selection based on known phenotypes:

  • Locomotor activity assessments: Home cage monitoring and open field tests to capture hyperactivity

  • Prepulse inhibition testing: Essential for assessing sensorimotor gating deficits relevant to schizophrenia

  • Memory paradigms: Contextual fear conditioning and Barnes maze to evaluate hippocampal-dependent memory deficits

  • Emotional behavior tests: Elevated plus maze and forced swim tests to assess anxiety and depression-like behaviors

• Testing design considerations:

  • Use balanced sex distribution to account for potential sex differences

  • Include appropriate sample sizes (typically 8-15 mice per group) for adequate statistical power

  • Employ littermate controls to minimize genetic background effects

  • Conduct tests from least to most stressful to avoid carryover effects

  • Allow sufficient recovery periods between tests (typically 1-3 days)

• Standardization of conditions:

  • Maintain consistent testing time (considering circadian effects)

  • Control environmental factors (lighting, temperature, background noise)

  • Habituate animals to handling and testing rooms before experiments

  • Use automated systems when possible to minimize experimenter bias

• Complementary approaches:

  • Combine behavioral testing with in vivo microdialysis to assess dopamine release in relevant brain regions

  • Follow behavioral testing with electrophysiological recordings to correlate behavior with synaptic function

This comprehensive approach will yield the most reliable and interpretable data from CRMP1 mouse models.

What are the most effective methods for analyzing CRMP1 function at the cellular level?

Analyzing CRMP1 function at the cellular level requires multiple complementary approaches:

• Primary neuronal culture techniques:

  • Cortical and hippocampal neuron cultures from CRMP1-deficient and wild-type mice

  • Quantitative analysis of neurite outgrowth, including measurement of:

    • Neurite length and number

    • Branching complexity (Sholl analysis)

    • Growth cone morphology

    • Axon/dendrite differentiation

  • Time-lapse imaging to capture dynamic aspects of neurite extension and retraction

• Immunocytochemical analysis:

  • Co-labeling with cytoskeletal markers (tubulin, actin) to examine structural organization

  • Phospho-specific antibodies to assess CRMP1 activation state

  • Synaptic protein markers (PSD95, synapsin) to evaluate synaptogenesis

  • Dendritic marker analysis (MAP2) to assess dendritic integrity

• Biochemical approaches:

  • Protein oligomerization assays to examine CRMP1 complex formation

  • Co-immunoprecipitation to identify protein interaction partners

  • Western blotting to quantify protein levels and phosphorylation states

  • In vitro kinase assays to examine regulation by Cdk5, GSK3, and ROCK

• Molecular manipulation strategies:

  • Rescue experiments with wild-type or mutant CRMP1 constructs

  • Domain deletion/mutation analysis to identify functional regions

  • Acute knockdown approaches to bypass developmental compensation

  • Live-cell FRET imaging to monitor protein-protein interactions

These methods provide complementary information about CRMP1 function and can reveal how specific mutations or manipulations affect neuronal development at the cellular level.

How can researchers differentiate between CRMP1-specific effects and compensation by other CRMP family proteins?

Distinguishing CRMP1-specific effects from compensation by other CRMP family proteins requires strategic experimental approaches:

• Expression profiling:

  • Comprehensive qRT-PCR analysis of all CRMP family members in CRMP1-deficient tissues

  • Western blotting to detect potential upregulation of other CRMPs

  • Single-cell RNA sequencing to identify cell type-specific compensation patterns

  • Temporal analysis to detect when compensatory changes emerge during development

• Compound genetic approaches:

  • Generate double or triple knockout models (e.g., CRMP1/CRMP2 double knockout)

  • Use conditional knockout strategies to bypass developmental compensation

  • Create knockin models with specific mutations that disrupt particular functions

  • Compare phenotypes across different CRMP knockout lines

• Protein specificity techniques:

  • Develop and validate isoform-specific antibodies using knockout tissues as controls

  • Design domain-specific blocking peptides or antibodies

  • Use proximity labeling approaches to map CRMP1-specific interactomes

  • Perform in vitro competition assays with purified proteins

• Acute manipulation strategies:

  • Employ inducible knockdown or knockout systems to bypass developmental compensation

  • Use acute pharmacological inhibition with validated specificity

  • Perform acute rescue experiments with CRMP1-specific constructs

  • Utilize dominant-negative approaches that target specific CRMP1 functions

• Structure-function analysis:

  • Focus on unique domains or regions not conserved among CRMP family members

  • Identify CRMP1-specific post-translational modifications

  • Design mutations that specifically disrupt CRMP1 interactions without affecting other CRMPs

These approaches can help researchers distinguish genuine CRMP1-specific functions from effects due to compensatory mechanisms or functional redundancy within the CRMP family.

How should researchers interpret conflicting behavioral data in CRMP1 mouse models?

Interpreting conflicting behavioral data in CRMP1 mouse models requires systematic consideration of multiple factors:

• Experimental design variables:

  • Genetic background differences: CRMP1 phenotypes may vary across different background strains

  • Age-dependent effects: Some phenotypes may emerge only at specific developmental stages

  • Sex differences: Male and female mice may show distinct behavioral profiles

  • Testing environment: Laboratory conditions (lighting, noise, time of day) can significantly influence results

  • Handling methods: Different handling techniques can affect stress levels and behavioral outcomes

• Phenotypic interpretation frameworks:

  • Domain-specific analysis: Group behavioral tests by cognitive domain (e.g., learning, anxiety, social behavior)

  • Cross-test validation: Look for consistent patterns across multiple tests measuring similar constructs

  • Developmental trajectories: Consider how phenotypes evolve across development

  • Circuit-level interpretation: Link behavioral findings to known neural circuit alterations

• Methodological resolution approaches:

  • Standardize protocols across laboratories

  • Increase sample sizes to improve statistical power

  • Perform meta-analyses across multiple studies

  • Use automated testing systems to reduce experimenter bias

  • Implement blinded analysis procedures

• Integrated analysis strategies:

  • Correlate behavioral measures with molecular or cellular phenotypes

  • Apply multivariate statistical approaches to identify pattern clusters

  • Consider interactions between different behavioral domains

  • Examine individual variation and potential subgroups within genotypes

For example, the hyperactivity observed in CRMP1-deficient mice could be interpreted differently depending on context: as a schizophrenia-related positive symptom , as an anxiety-related phenotype, or as a general arousal abnormality. By evaluating patterns across multiple behavioral domains and correlating with neurobiological measures, researchers can develop more robust interpretations of seemingly conflicting data.

What statistical approaches are most appropriate for analyzing complex phenotypes in CRMP1 research?

Analyzing complex phenotypes in CRMP1 research requires sophisticated statistical approaches:

The appropriate statistical approach should be determined by the specific hypothesis, data structure, and experimental design. For example, in analyzing prepulse inhibition data from CRMP1-deficient mice treated with antipsychotics , a two-way repeated measures ANOVA with drug treatment and genotype as factors would be appropriate, followed by planned comparisons to test for drug-specific rescue effects.

How can researchers effectively reconcile in vitro and in vivo findings in CRMP1 research?

Reconciling differences between in vitro and in vivo findings in CRMP1 research requires systematic integration strategies:

• Bridging experimental approaches:

  • Implement ex vivo preparations (acute brain slices) as intermediate models

  • Develop more physiologically relevant in vitro systems (3D cultures, organoids)

  • Use the same readouts across in vitro and in vivo platforms when possible

  • Apply consistent analytical frameworks to both datasets

• Addressing systemic complexity factors:

  • Consider potential compensatory mechanisms present in vivo but absent in vitro

  • Account for developmental timing differences (acute vs. chronic effects)

  • Evaluate the influence of multiple cell types in vivo versus homogeneous cultures

  • Assess the impact of circuit-level effects present only in intact systems

• Methodological reconciliation strategies:

  • Perform parallel experiments with the same genetic manipulations

  • Use rescue experiments to confirm specificity in both systems

  • Apply dose-response studies to identify threshold effects

  • Implement time-course analyses to capture developmental dynamics

• Integrative analytical frameworks:

  • Develop computational models that incorporate both in vitro and in vivo parameters

  • Use systems biology approaches to map pathway interactions across models

  • Implement Bayesian integration methods to combine evidence from multiple sources

  • Apply translation validation approaches to verify key findings across systems

For example, the effects of CRMP1 variants on neurite outgrowth observed in cultured neurons can be reconciled with the dendritic organization abnormalities seen in vivo by:

• Comparing the molecular mechanisms (e.g., cytoskeletal interactions) in both systems

• Determining whether the same signaling pathways are involved

• Assessing whether the timing and magnitude of effects are comparable

• Identifying environmental factors present in vivo that might modulate the phenotype

How can CRMP1 mouse models inform our understanding of schizophrenia pathophysiology?

CRMP1 mouse models offer valuable insights into schizophrenia pathophysiology through multiple dimensions:

• Behavioral endophenotypes:

  • Hyperactivity in CRMP1-deficient mice parallels positive symptoms in schizophrenia

  • Impaired prepulse inhibition models sensorimotor gating deficits seen in patients

  • Cognitive deficits in these mice reflect the cognitive symptoms of schizophrenia

  • These behavioral abnormalities provide construct validity for the model

• Neurotransmitter system abnormalities:

  • Enhanced methamphetamine-induced dopamine release in the prefrontal cortex of CRMP1-deficient mice aligns with the dopamine hypothesis of schizophrenia

  • This finding suggests CRMP1 involvement in regulating mesocortical dopaminergic transmission

  • The normalization of prepulse inhibition deficits by chlorpromazine (a dopamine D2 receptor antagonist) strengthens this connection

  • These observations provide face validity and predictive validity for antipsychotic treatment

• Neurodevelopmental mechanisms:

  • CRMP1's role in neurite outgrowth and neuronal migration supports the neurodevelopmental hypothesis of schizophrenia

  • Structural abnormalities in dendritic organization in CRMP1-deficient mice may parallel cortical connectivity disruptions in schizophrenia

  • The synaptic protein abnormalities (reduced GAP-43 and PSD95) suggest mechanisms for altered synaptic function

• Translational implications:

  • CRMP1 alterations have been identified in individuals with schizophrenia

  • Studying downstream effects of CRMP1 dysfunction may reveal novel therapeutic targets

  • The model can be used to test experimental therapeutics targeting cytoskeletal regulation

  • Cross-species validation of findings strengthens translational relevance

• Integration with other schizophrenia models:

  • Comparing CRMP1 models with other genetic and environmental models can identify convergent pathways

  • Exploring interactions between CRMP1 and other schizophrenia risk genes may reveal mechanistic insights

  • Combining CRMP1 deficiency with environmental risk factors could develop more complete models

The table below summarizes key parallels between CRMP1 mouse phenotypes and schizophrenia symptoms:

What are the molecular mechanisms linking CRMP1 dysfunction to neurodevelopmental disorders?

The molecular mechanisms connecting CRMP1 dysfunction to neurodevelopmental disorders operate at multiple levels:

• Cytoskeletal regulation mechanisms:

  • CRMP1 regulates microtubule dynamics essential for neurite outgrowth and neuronal migration

  • CRMP1 variants identified in neurodevelopmental disorders affect protein oligomerization

  • Disruption of CRMP1-cytoskeleton interactions leads to abnormal neuronal morphology

  • These abnormalities likely underlie the dendritic organization defects observed in CRMP1-deficient mice

• Signaling pathway integration:

  • CRMP1 function is regulated by phosphorylation through kinases including Cdk5, GSK3, and ROCK

  • These kinases represent convergence points for multiple signaling pathways implicated in neurodevelopmental disorders

  • CRMP1 dysfunction may disrupt the integration of guidance cues and growth factors during development

  • The spatiotemporal regulation of these pathways is critical for proper circuit formation

• Synaptic development and plasticity:

  • CRMP1 contributes to dendritic spine formation and maturation

  • CRMP1-deficient mice show reduced expression of synaptic proteins like GAP-43 and PSD95

  • These synaptic abnormalities likely contribute to the LTP deficits observed in these mice

  • Synaptic dysfunction is a common feature across neurodevelopmental disorders

• Genetic evidence:

  • De novo CRMP1 variants in humans cause muscular hypotonia, intellectual disability, and/or autism spectrum disorder

  • These variants affect highly conserved regions of the protein and disrupt CRMP1 structure

  • Functional analysis shows that these variants affect neurite outgrowth in cortical neurons

  • Maternal CRMP1 autoantibodies have been associated with autism in offspring

• Network-level disruptions:

  • Alterations in CRMP1 function disrupt the balance of excitatory and inhibitory connections

  • The hyperactivity phenotype in CRMP1-deficient mice may reflect circuit-level imbalances

  • Abnormal mesocortical dopaminergic transmission suggests broader network dysfunction

  • These network perturbations likely contribute to cognitive and behavioral abnormalities

Understanding these molecular mechanisms provides opportunities for therapeutic intervention in neurodevelopmental disorders associated with CRMP1 dysfunction, potentially through targeted approaches that restore cytoskeletal regulation, synaptic function, or specific signaling pathways.

How can cutting-edge techniques enhance our understanding of CRMP1 function in neural development?

Cutting-edge techniques are revolutionizing our understanding of CRMP1 function in neural development:

• Advanced genetic engineering approaches:

  • CRISPR-Cas9 genome editing for creating precise CRMP1 mutations that mimic human variants

  • Conditional knockout strategies using Cre-lox systems for temporal and cell type-specific CRMP1 deletion

  • Knockin of fluorescently tagged CRMP1 at endogenous loci for live imaging

  • Base editing for introducing specific point mutations without double-strand breaks

  • These approaches enable more precise manipulation of CRMP1 function in vivo

• High-resolution imaging technologies:

  • Super-resolution microscopy (STORM, PALM) to visualize CRMP1 localization at nanoscale resolution

  • Two-photon imaging to monitor CRMP1-expressing neurons in the intact brain

  • Light-sheet microscopy combined with tissue clearing for whole-brain mapping of CRMP1 expression

  • Live imaging of fluorescently tagged CRMP1 to track its dynamics during neurite outgrowth

  • These techniques provide unprecedented spatial and temporal resolution of CRMP1 localization and function

• Single-cell and multi-omics approaches:

  • Single-cell RNA sequencing to identify cell populations with unique CRMP1 expression patterns

  • Spatial transcriptomics to map CRMP1 expression within tissue architecture

  • Cell type-specific proteomics to identify CRMP1 interaction partners in different neuronal populations

  • Multi-modal analysis combining transcriptomics, proteomics, and epigenomics

  • These methods reveal cell type-specific functions and regulatory mechanisms

• Structural biology and protein interaction analysis:

  • Cryo-electron microscopy to determine high-resolution structures of CRMP1 complexes

  • Hydrogen-deuterium exchange mass spectrometry to map conformational changes

  • In-cell NMR to study CRMP1 structure and interactions in living cells

  • Proximity labeling approaches (BioID, APEX) to map the CRMP1 interactome

  • These techniques provide detailed insights into how CRMP1 variants disrupt protein structure and function

• Functional circuit analysis:

  • Optogenetics to manipulate CRMP1-expressing neurons with temporal precision

  • Chemogenetics for sustained modulation of specific neuronal populations

  • Fiber photometry to monitor activity of CRMP1-positive neurons during behavior

  • Connectomics approaches to examine circuit alterations in CRMP1-deficient mice

  • These methods link molecular mechanisms to circuit-level phenotypes

The integration of these cutting-edge techniques allows researchers to build a comprehensive understanding of CRMP1 function across multiple scales, from molecular interactions to circuit-level consequences, ultimately enhancing our knowledge of how CRMP1 dysfunction contributes to neurodevelopmental disorders.

What are common challenges in phenotyping CRMP1 mouse models and how can they be addressed?

Researchers face several challenges when phenotyping CRMP1 mouse models, each requiring specific solutions:

• Behavioral phenotyping challenges:

  • Variable penetrance of phenotypes

  • Influence of testing environment and experimenter

  • Potential confounding by general health issues

  • Difficulty detecting subtle behavioral abnormalities

  Solutions:

  • Increase sample sizes to account for variability

  • Implement standardized testing protocols with environmental controls

  • Use automated testing systems to reduce experimenter bias

  • Conduct comprehensive health assessments before behavioral testing

  • Employ sensitive assays designed to detect specific phenotypes of interest

• Molecular and cellular analysis challenges:

  • Antibody cross-reactivity with other CRMP family members

  • Potential compensatory upregulation of other CRMPs

  • Regional and temporal heterogeneity in CRMP1 expression

  • Difficulty isolating specific cell populations

  Solutions:

  • Validate antibodies using CRMP1 knockout tissue as negative controls

  • Assess expression of all CRMP family members

  • Perform detailed spatiotemporal analysis of expression patterns

  • Use cell type-specific isolation techniques (FACS, laser capture microdissection)

• Electrophysiological assessment challenges:

  • Variability in LTP protocols across laboratories

  • Difficulty linking cellular phenotypes to behavioral outcomes

  • Age-dependent changes in synaptic plasticity

  • Technical challenges in maintaining stable recordings

  Solutions:

  • Standardize recording protocols and conditions

  • Perform recordings in behaviorally characterized animals

  • Conduct age-dependent analyses

  • Implement quality control criteria for recording stability

• Genetic background issues:

  • Influence of genetic background on phenotypic expression

  • Potential flanking gene effects

  • Background-specific modifier genes

  Solutions:

  • Maintain colonies on well-defined genetic backgrounds

  • Use littermate controls consistently

  • Consider backcrossing to multiple backgrounds for comparison

  • Implement congenic strain development for critical experiments

• Translational relevance challenges:

  • Species differences in CRMP1 function and expression

  • Limited availability of human samples for validation

  • Difficulty modeling complex human disorders

  Solutions:

  • Compare mouse findings with human genetic and postmortem studies

  • Utilize human iPSC-derived neurons carrying CRMP1 variants

  • Focus on conserved cellular mechanisms rather than exact behavioral phenotypes

  • Consider humanized mouse models for specific variants

By systematically addressing these challenges, researchers can enhance the reliability and translational relevance of findings from CRMP1 mouse models, advancing our understanding of CRMP1's role in brain development and disease.

How can researchers design experiments to distinguish direct CRMP1 effects from secondary consequences?

Distinguishing direct CRMP1 effects from secondary consequences requires carefully designed experimental strategies:

• Temporal manipulation approaches:

  • Implement inducible knockout/knockdown systems (e.g., tetracycline-controlled, tamoxifen-inducible)

  • Design time-course experiments to establish causality sequences

  • Use acute pharmacological inhibition to bypass developmental adaptations

  • Perform developmental stage-specific manipulations

  These approaches can separate immediate CRMP1 actions from long-term adaptive changes.

• Spatial and cell type-specific strategies:

  • Utilize conditional knockout models targeting specific cell types or brain regions

  • Implement sparse manipulation techniques (e.g., in utero electroporation) to affect subsets of cells

  • Compare cell-autonomous versus non-cell-autonomous effects through chimeric approaches

  • Use viral vectors for localized manipulation in mature circuits

  These methods help isolate CRMP1 functions in specific cellular contexts.

• Molecular specificity techniques:

  • Design structure-function studies with domain-specific mutations

  • Create separation-of-function mutants that disrupt specific interactions

  • Use protein replacement strategies (knockout plus rescue with mutant variants)

  • Implement rapid protein degradation systems (e.g., auxin-inducible degron)

  Such approaches enable attribution of phenotypes to specific molecular functions of CRMP1.

• Direct versus indirect interaction analysis:

  • Employ proximity labeling approaches (BioID, APEX) to identify direct interaction partners

  • Implement in vitro reconstitution assays with purified components

  • Use FRET/FLIM to detect direct protein interactions in living cells

  • Apply cross-linking mass spectrometry to map interaction interfaces

  These techniques distinguish direct CRMP1 binding partners from components of larger complexes.

• Pathway dissection strategies:

  • Conduct epistasis experiments combining CRMP1 manipulation with pathway activators/inhibitors

  • Implement phospho-proteomic analyses to identify signaling consequences

  • Use pharmacological rescue approaches targeting downstream effectors

  • Perform gene expression profiling at multiple time points after CRMP1 manipulation

  These approaches clarify where CRMP1 functions within signaling cascades.

For example, to determine whether dendritic organization defects are direct CRMP1 effects or secondary to altered activity, researchers could combine conditional CRMP1 knockout with activity manipulations (e.g., DREADDs or optogenetics) to dissociate these variables. Similarly, acute CRMP1 inhibition in mature neurons can distinguish developmental versus maintenance functions.

What are promising future directions for CRMP1 research in neurodevelopmental disorders?

Several promising directions will advance CRMP1 research in neurodevelopmental disorders:

• Human genetics and disease modeling:

  • Expanded screening for CRMP1 variants in neurodevelopmental disorder cohorts

  • Development of patient-derived iPSC models carrying specific CRMP1 variants

  • Creation of knock-in mouse models with exact human disease mutations

  • Comparative analysis across species to identify conserved disease mechanisms

  These approaches will strengthen the connection between CRMP1 dysfunction and human disorders.

• Circuit-level analysis:

  • Implementation of whole-brain activity mapping in CRMP1 mouse models

  • Circuit-specific manipulation of CRMP1 in behaviorally relevant pathways

  • In vivo calcium imaging during cognitive and social tasks

  • Cross-species validation of circuit abnormalities

  Such studies will bridge molecular mechanisms and behavioral outcomes.

• Therapeutic development:

  • High-throughput screening for modulators of CRMP1 function or downstream pathways

  • Development of targeted approaches to restore cytoskeletal regulation

  • Exploration of critical periods for intervention in CRMP1-related disorders

  • Testing of combinatorial therapies targeting multiple aspects of CRMP1 pathophysiology

  These efforts may lead to novel treatments for CRMP1-associated conditions.

• Multi-omics integration:

  • Single-cell multi-modal analysis linking CRMP1 to gene regulatory networks

  • Spatial transcriptomics to map CRMP1-dependent changes across development

  • Systems biology approaches to position CRMP1 within broader neurodevelopmental pathways

  • Computational modeling to predict outcomes of CRMP1 manipulation

  These integrative approaches will contextualize CRMP1 within complex biological systems.

• Interaction with environmental factors:

  • Examination of gene-environment interactions affecting CRMP1 function

  • Investigation of epigenetic regulation of CRMP1 in response to environmental challenges

  • Study of CRMP1 involvement in stress response pathways

  • Analysis of how early life experiences modify CRMP1-dependent development

  This research will help explain variability in CRMP1-associated phenotypes.

• Extended phenotyping:

  • Investigation of sensory processing abnormalities in CRMP1 models

  • Assessment of sex-specific phenotypes and mechanisms

  • Longitudinal studies capturing developmental trajectories

  • Examination of aging-related phenotypes in CRMP1-deficient animals

  Broader phenotyping will reveal the full spectrum of CRMP1's biological roles.

By pursuing these directions, researchers can develop a comprehensive understanding of how CRMP1 dysfunction contributes to neurodevelopmental disorders and identify potential therapeutic strategies for affected individuals.