Recombinant Mouse Meteorin (Metrn)

What is Mouse Meteorin and what are its primary biological functions?

Mouse Meteorin (Metrn) is a secreted protein involved in both glial cell differentiation and axonal network formation during neurogenesis. It plays critical roles in promoting astrocyte differentiation and transforming cerebellar astrocytes into radial glia. Additionally, Meteorin induces axonal extension in small and intermediate neurons of sensory ganglia by activating nearby satellite glia . This protein belongs to the meteorin family and is also known by alternative names including Hyrac and Hypoxia/reoxygenation regulatory factor .

For researchers seeking to study these functions, it's essential to use properly validated recombinant protein with confirmed biological activity. When designing experiments, consider that Meteorin's effects may vary depending on the neural cell type and developmental stage being examined.

How does Mouse Meteorin's amino acid sequence and structure influence its functionality?

Recombinant Mouse Meteorin protein typically encompasses amino acids 22-291 of the full sequence . The functional domains within this range are responsible for its ability to interact with target receptors and initiate signaling cascades in neural cells. The calculated molecular weight of the native protein is approximately 30 kDa , though this may appear different on SDS-PAGE depending on post-translational modifications and tags used in the recombinant form.

When planning experiments, researchers should consider:

• Using full-length protein (aa 22-291) for most functional studies

• Being aware that truncated versions may have altered biological activities

• Accounting for the effects of fusion tags (such as Fc or His) on protein function

What expression systems yield the most biologically active Recombinant Mouse Meteorin?

Recombinant Mouse Meteorin has been successfully expressed in various systems, with insect cells and mammalian cells being the most common. Insect cell-expressed Meteorin typically achieves >90% purity with endotoxin levels <1 EU/μg , making it suitable for most in vitro applications. For studies requiring protein with mammalian-type post-translational modifications, HEK293 cell expression systems are preferred .

When selecting a recombinant protein for your research:

• Consider whether post-translational modifications are critical for your study

• Verify the purity (typically >85-90% by SDS-PAGE)

• Check endotoxin levels, especially for cell-based assays and in vivo studies

• Assess biological activity using functional assays relevant to your research

What are the optimal reconstitution and storage conditions for Recombinant Mouse Meteorin?

To maintain the biological activity of lyophilized Recombinant Mouse Meteorin:

• Reconstitution should typically be performed in sterile PBS, pH 7.4. Some commercial preparations include protectants such as trehalose, mannitol, and 0.01% Tween 80 .

• For storage recommendations:

  • Lyophilized protein is generally stable for up to 12 months when stored at -20°C to -80°C

  • Reconstituted protein solution can be stored at 4-8°C for 2-7 days

  • For longer-term storage of reconstituted protein, create aliquots and store at -20°C or lower for up to 3 months

  • Avoid repeated freeze-thaw cycles

Researchers should always refer to the specific storage and reconstitution information provided by the manufacturer, as formulations may vary between suppliers.

How can researchers validate the activity of Recombinant Mouse Meteorin in experimental systems?

Biological activity validation of Recombinant Mouse Meteorin should include:

• Functional assays:

  • Astrocyte differentiation assays using neural progenitor cells

  • Radial glia transformation assays using cerebellar astrocytes

  • Axonal extension measurement in sensory neuron cultures

• Molecular validation:

  • Western blotting to confirm molecular weight and immunoreactivity

  • SDS-PAGE analysis to verify purity

  • Mass spectrometry for detailed characterization

• Signaling pathway verification:

  • Phosphorylation status of downstream targets

  • Analysis of gene expression changes in responsive cells

When reporting research findings, include detailed validation methods to enhance reproducibility across laboratories.

What are appropriate positive and negative controls for Meteorin-related experiments?

For robust experimental design when studying Meteorin:

Positive controls:

• Commercially validated Recombinant Mouse Meteorin with known activity

• Cell lines with confirmed Meteorin responsiveness (e.g., certain astrocyte or neural progenitor lines)

• Tissues with known high Meteorin expression (developing nervous system)

Negative controls:

• Heat-inactivated Meteorin protein (95°C for 10 minutes typically denatures protein structure)

• Isotype-matched irrelevant proteins of similar size

• Meteorin-knockout cells or tissues (if available)

• Specific inhibitors of known Meteorin signaling pathways

Implementing these controls helps distinguish specific Meteorin effects from non-specific experimental artifacts.

How does Meteorin contribute to glial-neuronal interactions during development and disease?

Meteorin serves as a critical mediator of glial-neuronal communication during development. Research indicates that Meteorin secreted by neural progenitors and glial cells influences:

• Developmental processes:

  • Promotes astrocyte differentiation from neural progenitors

  • Transforms cerebellar astrocytes into radial glia, which provide scaffolding for neuronal migration

  • Induces axonal extension in sensory neurons via activation of satellite glia

• Potential disease relevance:

  • Meteorin pathway dysfunction may contribute to neurodevelopmental disorders

  • The protein has been identified as a novel therapeutic target for wet age-related macular degeneration

  • Related family member Meteorin-like (METRNL) shows decreased levels in acute coronary syndrome, suggesting potential biomarker applications

When designing experiments to study these interactions, researchers should consider:

• Co-culture systems of neurons and glia

• Conditional knockout models with cell-type specific deletion

• Temporal regulation of Meteorin expression to distinguish developmental versus homeostatic roles

What signaling pathways are activated by Meteorin in different neural cell populations?

Current research indicates that Meteorin activates distinct signaling cascades depending on the cellular context:

• In glial cells:

  • Promotes astrocyte differentiation through pathways that have yet to be fully characterized

  • Transforms cerebellar astrocytes into radial glia through mechanisms that may involve cytoskeletal reorganization

• In neurons:

  • Indirectly influences axonal extension in sensory neurons by activating nearby satellite glia

  • The precise receptor-mediated signaling remains an active area of investigation

• Related protein METRNL:

  • Improves glucose tolerance via the calcium-dependent AMPKα2 pathway

  • Increases phosphorylation of HDAC5, a transcriptional repressor of GLUT4

This represents a significant knowledge gap in the field, as the direct receptor(s) for Meteorin have not been definitively identified. Researchers investigating these pathways should employ phosphoproteomic approaches and specific pathway inhibitors to delineate the signaling cascades.

How do the functions of Mouse Meteorin compare to its human ortholog?

While the search results don't provide specific comparisons between mouse and human Meteorin, related research on Meteorin-like protein indicates high conservation of function across species. Mouse recombinant Meteorin has 87% sequence homology with rat Meteorin , suggesting evolutionary conservation of this protein family.

When translating mouse findings to human applications, researchers should:

• Perform sequence and structural comparisons between mouse and human Meteorin

• Validate key findings in human cell or tissue models when possible

• Consider species-specific differences in expression patterns and signaling partners

• Assess conservation of binding partners and downstream effectors

These considerations are particularly important when evaluating Meteorin as a potential therapeutic target for human diseases.

What evidence supports Meteorin as a therapeutic target for neurological and retinal diseases?

Emerging research indicates that Meteorin has therapeutic potential in several contexts:

• Retinal diseases:

  • Mouse recombinant Meteorin has been identified as a novel therapeutic target for wet age-related macular degeneration (AMD)

  • Meteorin regulates pathways associated with angiogenesis, oxidative stress, and neuroprotection in the retina

• Metabolic conditions:

  • While not Meteorin itself, the related protein Meteorin-like (METRNL) improves glucose tolerance in both skeletal muscle cells and mice

  • METRNL functions via the AMPKα2 pathway and represents a promising therapeutic candidate for glucose-related diseases like type 2 diabetes

• Cardiovascular applications:

  • METRNL levels decrease in acute myocardial infarction patients

  • Negative correlation exists between METRNL levels and time from chest pain onset to emergency department admission

When designing preclinical studies to evaluate therapeutic potential:

• Consider optimal delivery methods for recombinant protein

• Determine effective dosing regimens

• Evaluate both efficacy and safety parameters

• Assess potential immunogenicity of recombinant proteins

What methodological approaches are most effective for studying Meteorin's effects on neurogenesis?

To effectively investigate Meteorin's role in neurogenesis:

• In vitro systems:

  • Neural progenitor/stem cell cultures treated with recombinant Meteorin

  • Assessment of differentiation markers (GFAP for astrocytes, β-III tubulin for neurons)

  • Time-lapse imaging to track morphological changes

  • Co-culture systems to study glial-neuronal interactions

• Ex vivo approaches:

  • Organotypic slice cultures from developing brain regions

  • Explant cultures from sensory ganglia to study axonal extension

• In vivo models:

  • Conditional knockout/knockin mouse models

  • In utero electroporation for spatiotemporal manipulation of Meteorin expression

  • Viral vector-mediated delivery of Meteorin to specific brain regions

• Analytical techniques:

  • Immunocytochemistry/immunohistochemistry for cellular phenotyping

  • Transcriptomic analysis to identify Meteorin-regulated genes

  • Proteomics to characterize signaling pathways

These methodological approaches should be selected based on the specific research question and combined to provide complementary lines of evidence.

How should researchers address contradictory findings regarding Meteorin's effects in different experimental models?

When confronted with contradictory results across different experimental systems:

• Methodological considerations:

  • Compare protein quality and source (expression system, purity, endotoxin levels)

  • Assess activity validation methods used in different studies

  • Evaluate experimental readouts and their sensitivity/specificity

  • Consider differences in cell types, animal strains, and developmental stages

• Analytical approaches:

  • Perform meta-analysis of published data with standardized effect size calculations

  • Use systematic review methodology to identify factors contributing to variability

  • Consider Bayesian statistical frameworks to incorporate prior knowledge

• Reconciliation strategies:

  • Design experiments that directly compare conditions yielding contradictory results

  • Investigate context-dependent effects (dose, timing, cell type)

  • Examine potential interactions with other factors in the experimental system

Remember that apparent contradictions may reveal biologically meaningful context-dependency of Meteorin function rather than experimental error.

What challenges exist in quantifying Meteorin in complex biological samples?

Accurate quantification of Meteorin in biological samples presents several challenges:

• Technical considerations:

  • ELISA development requires validated antibody pairs with demonstrated specificity

  • Sample matrix effects may interfere with detection in complex samples like serum or tissue lysates

  • Distinguishing between endogenous and recombinant protein in experimental systems

• Biological considerations:

  • Post-translational modifications may affect antibody recognition

  • Potential binding to carrier proteins or receptors in biological fluids

  • Presence of proteolytic fragments with unknown immunoreactivity

• Standardization challenges:

  • Lack of universally accepted reference standards

  • Variation in antibody specificity between different commercial sources

  • Need for appropriate normalization strategies

Researchers should validate quantification methods using spike-recovery experiments, linearity-of-dilution tests, and comparison of multiple detection methods when possible.

How can researchers optimize experimental design to detect subtle phenotypic effects of Meteorin?

To detect subtle or context-dependent effects of Meteorin:

• Power analysis and sample size:

  • Conduct a priori power calculations based on expected effect sizes

  • Consider increasing sample sizes to detect small but biologically significant effects

  • Use paired designs when possible to reduce inter-individual variability

• Phenotypic assessment:

  • Employ multiple complementary readouts (morphological, molecular, functional)

  • Consider high-content analysis approaches for multiparametric phenotyping

  • Utilize time-course experiments to capture transient effects

• Experimental variability control:

  • Standardize experimental conditions (cell passage number, animal age, time of day)

  • Include appropriate positive controls with known effect sizes

  • Implement blinded analysis to prevent observer bias

  • Utilize batch controls across experimental runs

These optimizations are particularly important when studying Meteorin's effects on complex processes like glial differentiation or axonal extension, where phenotypic changes may be subtle or occur in subpopulations of cells.

How are multi-omics approaches enhancing our understanding of Meteorin biology?

Multi-omics strategies provide powerful tools for comprehensively characterizing Meteorin function:

• Transcriptomic approaches:

  • RNA-seq to identify genes regulated by Meteorin treatment

  • Single-cell transcriptomics to define cell-type specific responses

  • Analysis of temporal gene expression dynamics after Meteorin stimulation

• Proteomic methods:

  • Identification of Meteorin-interacting proteins through IP-MS

  • Phosphoproteomics to map signaling cascades activated by Meteorin

  • Spatial proteomics to determine subcellular localization of signaling components

• Metabolomic considerations:

  • Characterization of metabolic changes induced by Meteorin

  • Integration with transcriptomic data to identify regulated metabolic pathways

• Integrative bioinformatics:

  • Network analysis to identify regulatory hubs in Meteorin signaling

  • Comparative analysis across species to identify evolutionarily conserved mechanisms

  • Machine learning approaches to predict cell type-specific responses

These multi-omics approaches are particularly valuable for identifying unexpected or non-canonical functions of Meteorin that might be missed by hypothesis-driven research.

What are the most promising approaches for studying Meteorin's role in neurodevelopmental disorders?

To investigate Meteorin's potential contributions to neurodevelopmental disorders:

• Genetic approaches:

  • Analysis of METRN gene variants in patient cohorts

  • Creation of disease-relevant mutations in model systems using CRISPR/Cas9

  • Conditional knockout models with temporal and spatial specificity

• Human cellular models:

  • Patient-derived iPSCs differentiated to neural lineages

  • Brain organoids to study three-dimensional developmental processes

  • Isogenic cell lines with engineered mutations in Meteorin pathway components

• Functional assays:

  • Electrophysiological assessment of neuronal network development

  • Live imaging of neuronal migration and axon extension

  • Analysis of synaptic formation and function in the presence/absence of Meteorin

• Therapeutic exploration:

  • Rescue experiments using recombinant Meteorin in deficiency models

  • Combinatorial approaches targeting multiple components of affected pathways

  • Development of small molecule modulators of Meteorin signaling

These approaches should be integrated with clinical data to ensure translational relevance and identify patient populations most likely to benefit from Meteorin-targeted therapies.

What quality control parameters should researchers evaluate when selecting Recombinant Mouse Meteorin?

When selecting Recombinant Mouse Meteorin for research applications, evaluate:

• Purity specifications:

  • Minimum purity (typically >85-90% by SDS-PAGE)

  • Presence of contaminants or degradation products

  • Batch-to-batch consistency

• Endotoxin levels:

  • Should be <1.0 EU per μg of protein for cell culture applications

  • Lower levels (<0.1 EU/μg) may be required for sensitive primary cell cultures or in vivo studies

• Biological activity:

  • Validated through appropriate functional assays

  • Dose-response relationships established

  • Comparison to reference standards when available

• Physical parameters:

  • Appropriate molecular weight (approximately 30 kDa native; varies with tags)

  • Protein concentration accuracy

  • Aggregation status

• Production details:

  • Expression system used (insect cells, HEK293 cells)

  • Purification methodology

  • Presence and type of fusion tags (His, Fc, etc.)

Researchers should request detailed certificates of analysis and validation data from suppliers to ensure experimental reproducibility.

How does the presence of fusion tags affect the functionality of Recombinant Mouse Meteorin?

Fusion tags commonly used in Recombinant Mouse Meteorin production can impact functionality:

• Common tags and their impacts:

  • N-terminal Fc tags may aid solubility but can affect receptor binding

  • His-tags facilitate purification but may interfere with certain protein-protein interactions

  • GST tags can enhance stability but add significant molecular weight

• Experimental considerations:

  • When possible, compare tagged and untagged versions to assess tag effects

  • Consider tag removal using specific proteases if interference is suspected

  • Position tags (N- or C-terminal) based on known functional domains

• Documentation requirements:

  • Clearly report tag type, size, and position in publications

  • Specify whether tag was removed for functional studies

  • Note any controls performed to assess tag effects

The calculated molecular weight of Mouse Meteorin with an N-hFc tag is approximately 58.4 kDa, which appears as 57 kDa on SDS-PAGE , compared to the native protein at approximately 30 kDa . This significant difference highlights the importance of considering tag effects in experimental design and data interpretation.

How do Meteorin and Meteorin-like (METRNL) proteins differ in their biological functions?

While related, Meteorin and Meteorin-like (METRNL) exhibit distinct biological functions:

• Meteorin (METRN):

  • Primarily involved in glial cell differentiation and axonal network formation during neurogenesis

  • Promotes astrocyte differentiation and transforms cerebellar astrocytes into radial glia

  • Induces axonal extension in sensory neurons via activation of satellite glia

• Meteorin-like (METRNL):

  • Functions as a myokine/adipokine with metabolic effects

  • Improves glucose tolerance in skeletal muscle cells and mice

  • Acts through the calcium-dependent AMPKα2 pathway

  • Increases phosphorylation of HDAC5, affecting GLUT4 transcription

  • Shows decreased levels in acute coronary syndrome patients

When designing studies involving these proteins:

• Use specific antibodies validated to distinguish between METRN and METRNL

• Consider potential overlapping functions in certain tissues

• Recognize that knockout models for one may not reveal functions of the other

This functional divergence highlights the importance of specificity in experimental approaches and interpretation of results.

What insights can be gained from comparative analysis of Meteorin expression and function across species?

Comparative analysis across species provides valuable insights into Meteorin biology:

• Sequence conservation:

  • Mouse recombinant Meteorin has 87% sequence homology with rat Meteorin

  • Human and mouse orthologs likely share conserved functional domains

  • Differences in non-conserved regions may relate to species-specific functions

• Expression patterns:

  • Compare developmental timing of expression across species

  • Identify conserved versus divergent tissue expression patterns

  • Analyze regulatory elements controlling expression

• Functional conservation:

  • Test whether mouse recombinant Meteorin can activate signaling in human cells

  • Compare dose-response relationships across species

  • Identify species-specific binding partners or downstream effectors

• Evolutionary implications:

  • Analyze positive selection signatures in the Meteorin gene family

  • Correlate functional differences with evolutionary distance

  • Identify potential co-evolution with receptor partners

This comparative approach is particularly valuable for translational research, helping to predict whether findings in mouse models will extend to human biology and therapeutic applications.

Data Table 1: Comparison of Recombinant Mouse Meteorin Preparations

Data Table 2: Biological Functions of Meteorin in Neural Development