Armenian Hamster IgG Isotype Control [Clone PIP] — Purified in vivo GOLD™ Functional Grade

Clone PIP, associated with prolactin-inducible protein, is primarily used in in vivo mouse studies to investigate its roles in immunity, cancer progression, and host defense. While specific applications might vary, using clone PIP involves employing both PIP knockout mice and syngeneic murine tumor models with PIP-expressing cell lines. These models are crucial for understanding biological functions by manipulating PIP expression in mouse models.

However, the term "clone PIP" in the context of Armenian Hamster IgG Isotype Control also suggests its use as a negative control in experiments. This isotype control is tested against various species' cells and tissues to ensure minimal cross-reactivity, making it useful for distinguishing non-specific background signals from specific antibody signals.

Here is a summary of common applications:

• Immunity and Host Defense: Understanding how PIP influences immune responses.
• Cancer Progression: Investigating the role of PIP in cancer development using tumor models.
• Isotype Control: Employing Armenian Hamster IgG Isotype Control for negative control in antibody-based studies.

Commonly used antibodies or proteins studied alongside PIP in the literature depend on which "PIP" is being referenced, as the acronym can refer to several entities in biomedical research. Below are the most common contexts and co-used antibodies or proteins:

1. Phosphatidylinositol Phosphates (PIPs, e.g., PI(4)P, PI(4,5)P2)

• Common antibodies used together:
  • Anti-PIP monoclonal antibodies (targeting different PIP variants, such as PI(4)P or PI(4,5)P2).
  • 4E10 monoclonal antibody (cross-reacts with some PIP species and cardiolipin).
  • Isotype controls (e.g., Armenian Hamster IgG) for specificity control.
  • Anti-phosphatidylinositol-specific phospholipase C antibodies (used for enzymology studies and to probe PIP cleavage).
• Frequently associated proteins:
  • Protein-lipid overlays ("PIP strip" methods):
    • Used to screen protein domains that bind PIPs, such as Pleckstrin Homology (PH) domains, FYVE domains, or ENTH domains.
  • Phosphoinositide-dependent proteins:
    • Examples include CAPS, Munc13, and synaptotagmin 1, which interact with PI(4,5)P2 in exocytosis studies.

2. Prolactin-Induced Protein (PIP, also called GCDFP-15) in Cancer and Immunology

• Common antibodies used together:
  • Anti-PIP antibodies (various monoclonal or polyclonal clones).
  • Apoptosis-related protein antibodies:
    • CRADD, DAPK1, CD40—used to assess cell death, signaling, or immune response in tissues where PIP/GCDFP-15 expression is relevant.
• Associated proteins in functional studies:
  • Secretory pathway markers (e.g., actin-binding proteins, markers for secretory breast carcinoma).

3. PIP Box Motif Interactions (PCNA-Interacting Protein motifs in DNA repair)

• Associated antibodies and proteins:
  • PCNA antibodies (to study protein-protein interactions at replication forks).
  • Alexa Fluor-conjugated secondary antibodies (for detection and visualization of PIP box-PCNA complexes).

Summary Table: Settings and Common Co-used Antibodies

Specific combinations depend on the research objective (e.g., studying lipid signaling, cancer biomarkers, or DNA repair mechanics). Experimental setups often include both target-specific and control antibodies to validate specificity and functional relevance.

Key findings from scientific literature citing "clone PIP" vary depending on the scientific field, with notable contributions in immunology, cancer biology, and molecular genetics:

• In immunology, clone PIP, often referring to an Armenian Hamster IgG isotype control, is used in research to validate flow cytometry and immunoassay experiments by ensuring specificity of antibody binding. These studies emphasize PIP's utility as an immunoregulatory control and its application in both innate and adaptive immunity research.

• In cancer and cell biology, Prolactin-Induced Protein (PIP) has been shown to regulate the proliferation of luminal A breast cancer cells and other cell lines. Notable findings include:

  • PIP knockdown leads to defects in cell adhesion, cytoskeletal assembly, protein secretion, and proliferation control, with cMYC and cJUN identified as central regulators in networks affected by PIP.
  • High PIP expression has been shown to increase the sensitivity of breast cancer cells to anti-cancer drugs, suggesting a potential therapeutic angle.

• In molecular genetics, mutations in the Pip interaction domain have revealed that specific regions are essential for heterodimerization with PU.1 and possibly for interactions between other interferon regulatory factor proteins. This finding advances the understanding of transcription factor interactions in gene regulation.

• Some citations reference the use of clone PIP in various experimental models to confirm antibody specificity and as functional grade isotype controls, reinforcing the reliability of experimental results in immunological assays and tumor transplant models.

Overall, the key scientific findings from clone PIP citations include its validation as a molecular control in immunology, its regulators and functional implications in cancer biology, and its critical interaction domains in genetics.

The dosing regimens for PIP (piperacillin) in mouse models vary significantly based on the infection severity, pathogen characteristics, and desired pharmacokinetic/pharmacodynamic outcomes. Research demonstrates that optimizing these regimens requires careful consideration of both the drug's properties and the specific experimental context.

Pharmacokinetic-Based Dosing Strategies

The most sophisticated approach to PIP dosing in mice involves modeling regimens that mimic human clinical exposure. For aztreonam and similar β-lactam antibiotics like piperacillin, the critical parameter is the time the drug concentration remains above the minimum inhibitory concentration (T>MIC). When establishing dosing regimens, researchers calculate schedules based on human pharmacokinetic data and then translate these to achieve comparable drug exposure in mice.

Standard Dosing Regimens in Infection Models

In infected rat models, which provide insights applicable to mouse studies, PIP has been administered at 120 or 240 mg/kg intravenously with three different frequency regimens: every 8, 6, or 4 hours. These varied frequencies allow researchers to evaluate how dosing intervals affect therapeutic efficacy against different pathogen susceptibilities.

The selection of appropriate dosing depends heavily on the pathogen's resistance profile. For susceptible organisms with an MIC of 4 μg/mL, moderate dosing regimens achieve therapeutic success, while resistant strains with MICs of 32 μg/mL or higher require more aggressive dosing schedules to maintain adequate T>MIC values. Researchers have successfully used subcutaneous administration at 640 mg/kg every 6 hours to achieve free maximum drug concentrations slightly higher than those in humans while maintaining therapeutically relevant exposure times.

Model-Specific Considerations

The choice of mouse strain influences dosing strategy. Inbred BALB/c mice are frequently selected because their limited genetic diversity results in less variation in drug metabolism between individual animals, allowing for smaller group sizes while maintaining statistical power. This consistency is particularly valuable when establishing pharmacokinetic/pharmacodynamic indices that will translate to clinical applications.

When designing dosing regimens, researchers must account for the fundamental metabolic differences between mice and humans. Mice typically exhibit faster drug clearance rates, necessitating higher doses per kilogram and more frequent administration compared to human regimens. However, because antimicrobials like PIP directly target pathogens rather than host metabolism, positive results in mouse models generally have higher rates of successful translation to clinical settings.