Anti-Mouse IFNAR-1 [Clone MAR1-5A3] — Purified in vivo GOLD™ Functional Grade

Clone MAR1-5A3 is widely used in vivo in mice to functionally block type I interferon (IFN) receptor signaling by specifically targeting the IFNAR-1 (interferon alpha/beta receptor subunit 1), without cell depletion.

Most common in vivo applications include:

• Transient inhibition of type I interferon responses: Used to prevent antiviral, antimicrobial, and antitumor effects mediated by IFN-α/β signaling, to study the biological roles of type I IFNs in infection, immunity, and pathology.
• Permissive infection models: By ablating the innate IFN response, MAR1-5A3 enables robust viral replication in otherwise resistant mouse strains, facilitating research in pathogenesis for flaviviruses (such as Zika, Dengue), vesicular stomatitis virus (VSV), and other viruses. This approach is critical for pre-clinical testing of vaccines and antiviral therapies.
• Maternal/fetal transmission studies: Used in pregnant dams to examine transmission, fetal pathology, and vaccine efficacy in models of congenital viral infection, especially Zika virus.
• Experimental models of immune regulation and autoimmunity: By blocking IFNAR1, the antibody enables studies on type I IFNs in models of inflammation, autoimmune disease, or cancer.

Typical in vivo protocols:

• Single intraperitoneal dose (e.g., 2 mg in adult wild-type mice) to saturate IFNAR1 and achieve transient blockade (half-life ~5 days)
• Lower doses (e.g., 0.2–0.5 mg) for specialized protocols such as pregnancy/fetal studies, or when targeting younger mice.
• Adjustments by strain, age, infection model, and maternal status as dosing needs will differ accordingly.

Summary Table:

Key points:

• MAR1-5A3 blocks but does not deplete IFNAR1-expressing cells.
• In vivo use is specific for research, not therapeutic, purposes.
• Alternate applications (e.g., flow cytometry, western blot, immunoprecipitation) use different concentrations and are not comparable to in vivo use.

The antibody has become an essential tool for studying in vivo effects and mechanisms of type I interferon signaling in mice.

Commonly Used Antibodies and Proteins with MAR1-5A3

MAR1-5A3 is a monoclonal antibody specific to mouse IFNAR1 (Interferon alpha/beta receptor 1) and is widely used to block Type I interferon (IFN-α/β) signaling in mice, both in vitro and in vivo. In research, MAR1-5A3 is often used in combination with other antibodies and proteins targeting different components of the interferon signaling pathway, as well as control antibodies, to dissect the roles of specific interferons.

Key Antibodies Used Alongside MAR1-5A3

The most frequently referenced companion antibodies are those that selectively block different subtypes of interferon, allowing researchers to parse the individual roles of IFN-α and IFN-β in immune responses. These include:

• TIF-3C5: A monoclonal antibody specific to mouse IFN-β, used to selectively block IFN-β signaling.
• HDβ-4A7: A monoclonal antibody targeting mouse IFN-α, enabling selective blockade of IFN-α signaling.

These antibodies are often used in combination with MAR1-5A3 to dissect the contributions of IFN-α, IFN-β, and the shared IFNAR1 receptor in various biological systems. For example, studies may administer MAR1-5A3, TIF-3C5, or HDβ-4A7 (together with appropriate isotype controls) to compare the effects of global Type I IFN receptor blockade versus specific IFN-α or IFN-β blockade.

Isotype Controls

In experimental designs, isotype control antibodies (e.g., GIR-208, PIP, or an IgG2a mAb specific to dengue virus prM protein) are commonly administered alongside MAR1-5A3, TIF-3C5, and HDβ-4A7 to control for non-specific effects of antibody administration.

Other Proteins and Reagents

• IFNAR2: Though MAR1-5A3 targets IFNAR1, the functional Type I IFN receptor is a heterodimer of IFNAR1 and IFNAR2. Thus, the presence and function of IFNAR2 are often examined in the broader context of MAR1-5A3 studies.
• Type I IFNs (IFN-α, IFN-β): These are the natural ligands for the IFNAR1/IFNAR2 complex and are often used as positive controls or stimuli in functional assays where MAR1-5A3 is employed as a blocking antibody.
• Cytokine Bioassay Reagents: For evaluating neutralization, bioassays often involve L929 cells and encephalomyocarditis virus (EMCV) as a readout for Type I IFN activity.

Table: Common Companion Antibodies and Their Targets

Summary

MAR1-5A3 is frequently paired with antibodies such as TIF-3C5 (anti-IFN-β) and HDβ-4A7 (anti-IFN-α) to selectively block specific interferon subtypes, helping to delineate their individual contributions to immune responses. Isotype control antibodies are used to control for non-specific effects, and the broader context often includes IFNAR2 and the ligands IFN-α and IFN-β as part of the experimental system. These reagents are core to studies aimed at understanding the complex roles of Type I interferons in immunity, infection, and autoimmunity.

Key Scientific Findings from MAR1-5A3 Citations

Clone MAR1-5A3 is a well-characterized monoclonal antibody that specifically blocks the mouse type I interferon receptor (IFNAR1). It has become a central tool for studying type I interferon (IFN-I) signaling and for developing mouse models of viral infection. Here are the main findings from the scientific literature that cite MAR1-5A3:

Mechanisms of Action and Experimental Uses

• Receptor Blockade: MAR1-5A3 binds the extracellular domain of mouse IFNAR1, effectively blocking type I interferon signaling, which is crucial for antiviral, anti-microbial, anti-tumor, and immune regulatory responses.
• Model Establishment: It is widely used to transiently block IFN-I signaling in vivo, creating permissive infection models for a range of flaviviruses, such as West Nile virus (WNV), Zika virus (ZIKV), dengue virus (DENV), and Usutu virus (USUV).
• Dosing and Pharmacokinetics: The antibody’s dosing regimen depends on mouse strain, age, and experimental context. A standard intraperitoneal dose of 2 mg per adult wild-type mouse can saturate the IFNAR1 receptor pool, yielding a half-life of approximately 5.2 days. Lower doses (0.2–0.5 mg/mouse) have been used in pregnancy models, altering the duration and potency of blockade. Dosing affects viral load and pathogenesis; higher doses can enhance viral replication and disease severity in some models.

Biological Outcomes in Various Models

• Enhanced Viral Replication: MAR1-5A3 pre-treatment strongly enhances viremia and viral replication of several flaviviruses in wild-type mice, which are normally resistant to infection. For example, it enables lethal disease by certain flavivirus strains (e.g., African ZIKV strain Dakar 41525) that would otherwise cause only low-level viremia.
• Age and Strain Dependence: Viral replication is more sustained in younger mice than in older mice, and the outcome of infection can vary with viral strain, passage history, and inoculation route.
• No Universal Disease Induction: While MAR1-5A3 promotes viral replication, it does not always lead to overt disease—e.g., some DENV and ZIKV strains replicate but do not cause weight loss or neurologic disease unless specific conditions are met.
• Limited Blood-Brain Barrier Penetration: The antibody does not cross the blood-brain barrier efficiently, so neurovirulence in these models is attributed to enhanced invasion and replication of the virus within the CNS rather than direct antibody effects in the brain.
• Maternal-Fetal Transmission: In pregnancy models, blockade with MAR1-5A3 can facilitate transplacental viral transmission, and higher antibody doses correlate with increased fetal viral load.

Applications in Immunology and Therapy

• Vaccine and Antiviral Evaluation: MAR1-5A3-treated mice serve as tractable models for high-throughput evaluation of next-generation vaccines and antiviral interventions, especially for viruses that do not naturally infect wild-type mice.
• Role in Persistent Infection: Blockade of IFNAR1 signaling can alter the course of persistent viral infections, with complex effects on viral control and immune responses.
• Immunomodulation: Early blockade of type I IFN signaling has been shown to improve the efficacy of viral vaccines in some contexts, highlighting the dual role of IFN-I in both antiviral defense and immune regulation.
• Fc-Engineered Variants: Recombinant, Fc-silenced versions of MAR1-5A3 (e.g., MAR1-5A3-CP056) have been developed to eliminate Fc-mediated effector functions, improving specificity and reproducibility for research and potential therapeutic applications.

Summary Table: Major Findings and Model Outcomes

Conclusion

MAR1-5A3 is a versatile and widely cited tool for dissecting type I interferon biology, enabling the study of viral pathogenesis, immune responses, vaccine efficacy, and maternal-fetal transmission in mice. Its use has revealed that transient IFN-I blockade can both promote viral replication and reshape immune outcomes, with effects that are highly dependent on viral strain, host age, and experimental design. These findings underscore the antibody’s value in basic and translational immunology.

Dosing regimens of clone MAR1-5A3 (anti-mouse IFNAR-1 antibody) vary across mouse models depending on strain, age, infection context, therapeutic or experimental goal, and administration route, with common single doses ranging from 0.2 mg to 2.5 mg per mouse intraperitoneally, and maintenance regimens or repeated treatments applied in some chronic studies.

Essential context and supporting details:

• Single high-dose regimens (commonly 2 mg/mouse i.p.) are typical for transient blockade, such as infection model setups in wild-type adult mice, for example in studies of flavivirus or dengue virus susceptibility. These doses are considered saturating to block IFNAR1 signaling for up to 5 days, with efficacy potentially influenced by mouse age and body weight.

• Repeated or maintenance dosing is used for chronic disease models or extended observation:

  • In lupus models (BXSB and MRL-Fas^lpr^ mice), MAR1-5A3 was given at 500 μg i.p. for 3 consecutive days, then 250 μg three times per week until experiment termination.
  • Another recommended regimen for prolonged blockade involves a loading dose of 2.5 mg/mouse i.p., followed by weekly maintenance doses of 0.5 mg/mouse. The half-life after high loading is approximately 5 days, dropping to ~1.5 days for sub-saturating low doses.

• Mouse strain and age impact dosing: Younger mice may show more robust responses to the antibody, and higher doses may be needed to saturate the receptor in older or larger mice.

• Pathogen challenge context: In infectious disease models, MAR1-5A3 is most often used as a pre-treatment to enhance viral replication, and the severity and outcomes can depend on factors such as viral strain, inoculation route, and age of the mice.

• Route of administration: Intraperitoneal (i.p.) injection is the most common, but intravenous routes may alter biodistribution, though practical dose volumes are lower for IV.

• Experimental variations: Some studies use lower or staggered doses (e.g., 500 μg initially, repeated at intervals), especially when modeling chronic disease or when sustained IFNAR1 blockade is required. In contrast, acute infection models typically use single high doses.

Summary of typical dosing regimens by context:

• In summary: Dose, frequency, and regimen are tailored to experimental needs, strain, age, and disease model, with most acute studies opting for saturating doses and chronic studies for repeat/maintenance dosing.

If you need dosing recommendations for a specific mouse strain or disease model, please provide further details.