PTX2 Mouse

What is PTX2 in mice and what are its primary functions?

PTX2 (Pentraxin-2) in mice, also known as serum amyloid P component (SAP/APCS), is a constitutive, antiinflammatory, innate immune plasma protein that plays critical roles in tissue repair and immune modulation. It functions as a phylogenetically conserved protein that typically forms homopentameric structures in blood and recognizes receptors of the innate immune system .

PTX2's specific binding abilities allow it to target sites where tissue injury has occurred, assisting in eliminating damaged tissue through non-inflammatory mechanisms . Research demonstrates that PTX2 has significant anti-fibrotic properties, with recombinant human PTX-2 (rhPTX-2) showing the ability to retard progression of chronic kidney disease in experimental models .

What are the common synonyms and alternative names for PTX2 in scientific literature?

When conducting literature searches or examining gene and protein databases, researchers should be aware of several alternative designations for PTX2:

• Pentraxin-2

• Serum amyloid P-component (SAP)

• Apcs (amyloid P component, serum)

• Sap

This nomenclature diversity is important to consider when designing comprehensive literature searches to ensure all relevant research is captured.

What is the molecular structure and characteristics of mouse PTX2?

QTDLKRKVFV FPRESETDHV KLIPHLEKPL QNFTLCFRTY SDLSRSQSLF SYSVKGRDNE LLIYKEKVGE YSLYIGQSKV TVRGMEEYLS PVHLCTTWES SSGIVEFWVN GKPWVKKSLQ REYTVKAPPS IVLGQEQDNY GGGFQRSQSF VGEFSDLYMW DYVLTPQDIL FVYRDSPVNP NILNWQALNY EINGYVVIRP RV

The protein requires appropriate storage conditions, including the addition of carrier proteins (0.1% HSA or BSA) for long-term stability and avoiding multiple freeze-thaw cycles .

How is PTX2 expression regulated in mouse models?

PTX2 expression in mice is regulated through complex mechanisms involving transcriptional control networks. While specific regulatory elements for PTX2 are not extensively described in the provided search results, research into related transcription factors indicates that gene expression in mouse models often involves domain-specific transcription factors that can establish expression boundaries .

In normal conditions, PTX2 is predominantly produced as a circulating plasma protein. When examining pathological conditions, particularly in kidney disease models, exogenously delivered rhPTX-2 has been detected in macrophages and tubular epithelial cells, suggesting these cells as potential targets for PTX2-based interventions .

What are the optimal methods for detecting and quantifying PTX2 in mouse samples?

For quantitative detection of PTX2 in mouse samples, sandwich ELISA (Enzyme-Linked Immunosorbent Assay) is a validated method with high specificity and sensitivity. Commercial ELISA kits for mouse PTX2/SAP detection have been developed for multiple sample types including:

• Serum

• EDTA Plasma

• Heparin Plasma

• Cell lysates

• Cell culture supernatants

These assays demonstrate good precision with coefficient of variation (CV) values typically between 4-7.3% across different concentration ranges:

When analyzing PTX2 by western blot, researchers should note that while the theoretical molecular weight is 24.6 kDa, the apparent molecular weight on SDS-PAGE is typically 28-40 kDa due to glycosylation patterns .

How should PTX2 samples be prepared and stored for optimal results?

For optimal results when working with mouse PTX2:

• Storage considerations:

  • Add a carrier protein (0.1% HSA or BSA) for long-term storage stability

  • Formulate in buffer containing 10% glycerol in Phosphate Buffered Saline (pH 7.4)

  • Avoid multiple freeze-thaw cycles that can degrade protein quality

• Sample processing:

  • For plasma collection, both EDTA and heparin anticoagulants are compatible with PTX2 detection

  • Maintain consistent sample handling procedures across experimental groups

  • Consider time-dependent changes in PTX2 levels when planning collection protocols

• Quality control:

  • Verify protein purity (>90% as determined by SDS-PAGE) for recombinant preparations

  • Include appropriate standards and controls in quantification assays

How does mouse PTX2 function in models of chronic kidney disease?

In mouse models of chronic kidney disease, particularly in Col4a3 mutant mice with Alport syndrome, recombinant human PTX-2 (rhPTX-2) demonstrates significant therapeutic potential through multiple mechanisms:

• Disease modification effects:

  • Retards progression of chronic kidney disease

  • Reduces blood markers of kidney failure

  • Enhances lifespan by approximately 20%

  • Improves histological indicators of disease

• Dual cellular targeting:

  • Counteracts macrophage activation to reduce inflammatory responses

  • Provides cytoprotective effects for renal epithelium

These findings suggest that rhPTX-2 may have therapeutic applications in chronic fibrotic diseases of the kidney, functioning through both anti-inflammatory and tissue-protective mechanisms that together contribute to disease amelioration.

What signaling pathways does PTX2 modulate in inflammatory and fibrotic conditions?

Computational analysis of genes regulated by rhPTX-2 has identified the transcriptional regulator c-Jun along with its activator protein-1 (AP-1) binding partners as central targets for PTX-2 function. Research demonstrates that PTX-2:

• Attenuates c-Jun and AP-1 activity

• Reduces expression of AP-1-dependent inflammatory genes in both monocytes and epithelial cells

This inhibition of the c-Jun/AP-1 signaling pathway appears to be a key mechanism underlying PTX-2's anti-inflammatory and anti-fibrotic effects. By suppressing this pathway, PTX-2 can reduce the expression of inflammatory mediators and extracellular matrix proteins that contribute to fibrotic disease progression .

How do PTX2 levels correlate with disease progression in fibrotic conditions?

Research indicates that circulating levels of PTX-2 are decreased in chronic human fibrotic diseases, suggesting an inverse correlation between PTX2 levels and disease severity . This relationship provides rationale for therapeutic approaches that supplement or restore PTX2 levels in fibrotic conditions.

What are the critical parameters for designing PTX2 intervention studies in mice?

When designing PTX2 intervention studies in mouse models, researchers should consider several critical parameters:

• Dosing considerations:

  • Determine optimal dose based on disease model and severity

  • Consider pharmacokinetic properties of the specific PTX2 preparation

  • Establish appropriate control groups receiving vehicle alone

• Administration timing:

  • Preventive protocols (administration before disease onset)

  • Therapeutic protocols (administration after disease establishment)

  • Duration of treatment required for measurable effects

• Route of administration:

  • Systemic administration for widespread effects

  • Local administration for targeted tissue effects

  • Consideration of half-life and tissue distribution

• Outcome measurements:

  • Histological assessment of tissue fibrosis and inflammation

  • Functional parameters relevant to the disease model

  • Molecular markers of PTX2 activity, including c-Jun/AP-1 signaling pathway components

How can researchers distinguish PTX2 effects from other pentraxin family members?

To distinguish PTX2 effects from other pentraxin family members in experimental settings:

• Use highly specific antibodies validated for PTX2 detection without cross-reactivity with other pentraxins

• Employ genetic approaches:

  • PTX2 knockout models to confirm loss-of-function effects

  • Selective PTX2 overexpression to validate gain-of-function observations

• Design rescue experiments:

  • Administer recombinant PTX2 to PTX2-deficient models

  • Compare effects with other pentraxin family members

• Utilize molecular approaches to verify pathway specificity:

  • Confirm c-Jun/AP-1 pathway modulation, which appears to be a relatively specific target for PTX2

  • Examine gene expression patterns unique to PTX2 intervention

How can PTX2 be utilized in studying epithelial-macrophage interactions in disease models?

PTX2 provides a valuable tool for studying epithelial-macrophage interactions in disease models due to its demonstrated effects on both cell types:

• Dual cellular targeting:

  • PTX2 has been detected in both macrophages and tubular epithelial cells when administered exogenously

  • It counteracts macrophage activation while simultaneously providing cytoprotective effects for the epithelium

• Experimental approaches:

  • Co-culture systems of epithelial cells and macrophages with PTX2 intervention

  • Tissue-specific knockout or overexpression of PTX2 to assess compartment-specific effects

  • Adoptive transfer of PTX2-modulated macrophages into disease models

• Mechanistic investigations:

  • Analyze c-Jun/AP-1 signaling in both cell types following PTX2 treatment

  • Examine cell-specific gene expression changes using single-cell RNA sequencing

  • Study paracrine signaling between epithelial cells and macrophages in the presence of PTX2

What are potential confounding factors when interpreting PTX2 research results?

Researchers should be aware of several potential confounding factors when interpreting PTX2-related experimental results:

• Terminology and identification challenges:

  • PTX2 can refer to different molecules (Pentraxin-2 vs. Pectenotoxin-2)

  • Multiple synonyms (SAP, Apcs) may complicate literature searches and data interpretation

• Methodological considerations:

  • Glycosylation patterns affect molecular weight determination (24.6 kDa theoretical vs. 28-40 kDa on SDS-PAGE)

  • Sample processing can affect PTX2 levels and detection

  • Antibody specificity may vary between assays and research groups

• Biological variability:

  • PTX2 is an acute phase protein with levels that fluctuate in response to inflammatory stimuli

  • Mouse strain differences may affect PTX2 expression and function

  • Age and sex differences can influence baseline PTX2 levels and responses

• Interpreting interventional studies:

  • When using recombinant PTX2, effects may depend on timing, dosage, and route of administration

  • Distinguishing direct PTX2 effects from secondary consequences requires careful experimental design

How does the amino acid sequence of mouse PTX2 compare to human PTX2 for translational research?

Understanding the differences and similarities between mouse and human PTX2 is crucial for translational research:

• Functional conservation:

  • Despite some sequence differences, mouse and human PTX2 share core functional domains

  • Recombinant human PTX-2 (rhPTX-2) demonstrates efficacy in mouse models of kidney disease, suggesting functional conservation across species

• Sequence analysis:

  • Mouse PTX2 contains 210 amino acids (residues 21-224) in its mature form

  • Key functional domains for receptor binding and immune modulation are conserved between species

• Translational considerations:

  • Cross-species activity allows for testing human recombinant PTX2 in mouse models

  • Species-specific differences in glycosylation patterns may affect protein stability and activity

  • Long-term administration of human PTX2 in mice may potentially induce anti-human protein immune responses