LIFR Mouse
Description
Oncology Studies
Immunization against LIFR in mouse mammary tumor models showed significant therapeutic potential:
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Tumor inhibition: LIFR immunization reduced tumor incidence to 25% (vs. 100% in controls) .
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Delayed tumor onset: Immunized mice exhibited slower tumor growth compared to controls .
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Mechanism: LIFR blockade inhibits signaling by LIF and related cytokines (e.g., oncostatin M, cardiotrophin-1), disrupting cancer stem cell maintenance .
| Study Parameter | Control Group | LIFR-Immunized Group |
|---|---|---|
| Tumor incidence | 100% | 25% |
| Median tumor appearance | 4 weeks | 6.5 weeks |
| Survival rate (3 months) | 0% | 75% |
Reproductive Biology
Conditional knockout studies revealed essential roles in uterine function:
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Implantation failure: Lifr-deficient mice showed 75% reduced embryo implantation rates .
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Epithelial specificity: LIFR expression in uterine luminal epithelium is critical for blastocyst attachment .
Therapeutic Development
Engineered LIFR variants demonstrate clinical promise:
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Ligand traps: Soluble LIFR-Fc fusion proteins with 20 pM affinity for LIF inhibit pancreatic tumor growth by 60% in xenograft models .
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Biological activity: Recombinant mouse LIFR (ED₅₀ ≤1 μg/mL) blocks LIF-mediated proliferation in erythroleukemic cells .
Recombinant Protein Production
Mouse LIFR is commercially available in multiple formats:
Antibody Tools for LIFR Research
Validated reagents enable precise detection and analysis:
Product Specs
The Leukemia Inhibitory Factor Receptor Alpha (LIFR) protein belongs to the Interleukin-6 receptor family. LIFR mediates the actions of various proteins, including IL-6, IL-11, IL-27, and Oncostatin M, influencing cell proliferation, differentiation, and survival throughout different life stages. LIFR expression is often downregulated in various breast cancer types, making it a potential prognostic marker.
Recombinant Mouse LIFR, produced in Baculovirus, is a single, glycosylated polypeptide chain. It consists of 794 amino acids (44-828 aa), resulting in a molecular weight of 89.6kDa. The LIFR protein is engineered with a 9 amino acid His tag at the C-terminus and undergoes purification using proprietary chromatographic techniques.
The LIFR protein solution has a concentration of 0.25mg/ml and is prepared in a solution containing 10% glycerol and Phosphate-Buffered Saline with a pH of 7.4.
For short-term storage (2-4 weeks), the product can be stored at 4°C. For extended storage, it is recommended to freeze the product at -20°C. Adding a carrier protein like HSA or BSA (0.1%) is advisable for long-term storage. It's important to minimize repeated freeze-thaw cycles to maintain product integrity.
The purity of the LIFR protein is determined by SDS-PAGE analysis and is greater than 90.0%.
The biological activity of LIFR is assessed based on its ability to inhibit the proliferation of TF-1 human erythroleukemic cells. The ED50 range, in the presence of Mouse LIF, is approximately less than or equal to 1ug/ml.
Leukemia inhibitory factor receptor, LIF receptor, LIF-R, D-factor/LIF receptor, CD118, CD antigen, leukemia inhibitory factor receptor isoform 1 precursor, Lifr.
Sf9, Baculovirus cells.
ADPLKRGVQD LKCTTNNMRV WDCTWPAPLG VSPGTVKDIC IKDRFHSCHP LETTNVKIPA LSPGDHEVTI NYLNGFQSKF TLNEKDVSLI PETPEILDLS ADFFTSSLLL KWNDRGSALP HPSNATWEIK VLQNPRTEPV ALVLLNTMLS GKDTVQHWNW TSDLPLQCAT HSVSIRWHID SPHFSGYKEW SDWSPLKNIS WIRNTETNVF PQDKVVLAGS NMTICCMSPT KVLSGQIGNT LRPLIHLYGQ TVAIHILNIP VSENSGTNII FITDDDVYGT VVFAGYPPDV PQKLSCETHD LKEIICSWNP GRITGLVGPR NTEYTLFESI SGKSAVFHRI EGLTNETYRL GVQMHPGQEI HNFTLTGRNP LGQAQSAVVI NVTERVAPHD PTSLKVKDIN STVVTFSWYL PGNFTKINLL CQIEICKANS KKEVRNATIR GAEDSTYHVA VDKLNPYTAY TFRVRCSSKT FWKWSRWSDE KRHLTTEATP SKGPDTWREW SSDGKNLIVY WKPLPINEAN GKILSYNVSC SLNEETQSVL EIFDPQHRAE IQLSKNDYII SVVARNSAGS SPPSKIASME IPNDDITVEQ AVGLGNRIFL TWRHDPNMTC DYVIKWCNSS RSEPCLLDWR KVPSNSTETV IESDQFQPGV RYNFYLYGCT NQGYQLLRSI IGYVEELAPI VAPNFTVEDT SADSILVKWD DIPVEELRGF LRGYLFYFQK GERDTPKTRS LEPHHSDIKL KNITDISQKT LRIADLQGKT SYHLVLRAYT HGGLGPEKSM FVVTKENSHH HHHH.
Q&A
What is LIFR and what is its structure in mice?
LIFR alpha (also known as LIFR beta or CD118) is a 190 kDa type I transmembrane protein belonging to the Interleukin-6 receptor family. In mice, mature LIFR alpha consists of a 785 amino acid extracellular domain (ECD) with two cytokine receptor homology domains, one WSxWS motif, and three fibronectin type III repeats, followed by a 25 amino acid transmembrane segment and a 239 amino acid cytoplasmic domain. Mouse LIFR shares 73% amino acid sequence identity with human LIFR and 90% with rat LIFR. Alternative splicing can generate a 90 kDa soluble form of the mouse LIFR ECD that retains ligand-binding activity .
What is the expression pattern of LIFR in mouse placenta during development?
LIFR is widely expressed in mouse placenta, particularly in the decidua, trophoblast giant cells, and syncytiotrophoblast layer. Immunofluorescence studies show that LIFR expression is highest at 13.5 days post-conception (dpc) and gradually decreases to 17.5 dpc, consistent with the expression pattern of Corticotropin-Releasing Hormone (CRH). Specifically, syncytiotrophoblast cells at 13.5 dpc show strong immunopositivity for LIFR, which diminishes as pregnancy progresses .
How does LIFR function in signal transduction?
LIFR binds LIF with low affinity, but this binding affinity increases significantly when LIFR associates with glycoprotein 130 (gp130). The LIFR/gp130 receptor complex activates Janus kinase (JAK) family proteins and downstream signaling through signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol 3-kinase (PI3K), and the ERK mitogen-activated protein kinase pathway. This complex also transduces Oncostatin M signals, although LIFR alone does not interact with Oncostatin M .
What mouse models are available for studying LIFR function?
Several mouse models have been developed for LIFR research:
| Model Type | Description | Application |
|---|---|---|
| Genetic knockout | Complete deletion of LIFR | Cancer progression studies, survival analysis |
| Conditional LIF knock-in | Inducible LIF overexpression | Studies of LIF effects on target tissues |
| Tissue-specific LIFR knockout | Targeted deletion in specific tissues | Dissecting tissue-specific roles (e.g., liver) |
| LIFR ligand trap | Engineered soluble LIFR decoy | Therapeutic inhibition of LIF signaling |
Genetic knockout of both LIFR copies significantly extends survival in pancreatic cancer mouse models . Conditional expression models allow for temporal control of LIF/LIFR signaling activation, which is valuable for studying acute versus chronic effects .
How should I administer recombinant LIF in mouse experiments?
For in vivo studies, intraperitoneal injection of recombinant LIF at doses ranging from 1-25 μg/kg body weight is effective. Experimental design should include dose-response studies, as different doses produce varying magnitudes of effect. For instance, maternal injection of LIF at 5 μg/kg body weight significantly increased placental CRH peptide levels within 3 hours, while a dose-dependent increase in Crh mRNA was observed at 1, 5, and 25 μg/kg doses .
For in vitro studies with mouse trophoblast stem cells (mTSCs), 10 ng/mL of LIF is commonly used to induce signaling .
What methods are recommended for detecting and quantifying LIFR expression?
Multiple complementary approaches should be employed:
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Protein level detection: Western blot analysis using specific antibodies against LIFR, with β-actin (42 kDa) as a loading control. Quantification can be performed by densitometry with results standardized to control samples .
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Cellular localization: Immunofluorescence staining of tissue sections with LIFR-specific antibodies and nuclear counterstaining (e.g., Hoechst 33342) .
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mRNA expression: Real-time RT-PCR for quantification of Lifr mRNA levels, with appropriate housekeeping genes for normalization .
How can LIFR mouse models be used to study cancer progression?
LIFR signaling has been implicated in promoting tumor progression, particularly in pancreatic cancer through KRAS-driven cell signaling. Research approaches include:
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Genetic manipulation: LIFR knockout in pancreatic cancer mouse models significantly extends survival, indicating its pro-tumorigenic role .
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Therapeutic inhibition: Engineered high-affinity soluble LIFR decoys (ligand traps) can sequester LIF and inhibit its signaling. An engineered LIFR-Fc fusion protein with ~50-fold increased affinity (~20 pM) compared to wild-type LIFR-Fc effectively blocks LIF-mediated effects in pancreatic cancer cells and slows xenograft tumor growth .
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Mechanistic studies: Investigating downstream signaling pathways activated by LIFR in specific cancer types to identify potential intervention points.
What is the role of LIFR in metabolic regulation and cachexia?
LIFR signaling plays a significant role in metabolic disorders, particularly cachexia:
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In transgenic mice with conditional LIF expression, systemic elevation of LIF induces cachexia by decreasing de novo lipogenesis and disrupting lipid homeostasis in the liver .
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Liver-specific LIFR knockout attenuates LIF-induced cachexia, demonstrating that LIFR-mediated changes in the liver contribute significantly to the cachexia phenotype .
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Mechanistically, LIF overexpression activates STAT3 to downregulate PPARα (a master regulator of lipid metabolism), leading to decreased expression of lipogenesis genes and reduced lipid synthesis in the liver .
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Activating PPARα with fenofibrate (a PPARα agonist) can restore lipid homeostasis and inhibit LIF-induced cachexia, offering potential therapeutic strategies .
What statistical approaches are appropriate for analyzing LIFR-related experimental data?
Based on published methodologies:
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Express data as mean ± standard error of the mean (SEM)
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Perform F test to determine equality of variances before selecting statistical tests
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For comparing two experimental groups, use unpaired two-tailed Student's t-test
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For multiple comparisons, employ ANOVA with Tukey post hoc test
Data analysis should be performed using appropriate software such as GraphPad Prism .
How should I interpret developmental changes in LIFR expression?
When analyzing developmental changes in LIFR expression, consider:
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Temporal patterns: In mouse placenta, LIFR protein levels peak at 13.5 dpc and decrease at 15.5 and 17.5 dpc, suggesting stage-specific functions .
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Spatial patterns: LIFR shows differential expression across placental cell types, with highest expression in syncytiotrophoblast cells at early stages .
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Co-expression analysis: The correlation between LIFR and functionally related proteins (e.g., CRH) can provide insights into signaling networks and biological relevance .
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Functional correlation: Changes in LIFR expression should be interpreted alongside developmental or physiological transitions in the tissue of interest.
How can I address inconsistent results in LIFR signaling experiments?
Inconsistent results may stem from several factors:
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Recombinant protein quality: Ensure the use of properly folded, biologically active recombinant LIF. The search results indicate using appropriately reconstituted recombinant mouse LIFR alpha protein from 0.2 μm filtered solutions in PBS .
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Receptor complexity: LIFR functions as part of heterodimeric complexes with gp130. Ensure both components are present and functional in your experimental system.
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Temporal dynamics: LIFR-induced signaling has time-dependent effects. For instance, LIF treatment induces Crh mRNA expression as early as 3 hours, while Pomc expression increases later (6-12 hours) .
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Tissue specificity: LIFR has distinct functions in different tissues. liver-specific LIFR knockout produces different outcomes than systemic manipulation .
What are the limitations of current LIFR mouse models?
Researchers should be aware of several limitations:
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Developmental compensation: Complete knockout models may trigger compensatory mechanisms through related receptors or pathways.
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Strain background effects: Mouse strain differences can influence phenotypes observed in LIFR studies.
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Translational gaps: While mouse LIFR shares significant homology with human LIFR (73% amino acid identity), species-specific differences in signaling or expression may exist .
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Context dependency: LIFR function varies dramatically based on physiological context, developmental stage, and disease state.
What emerging technologies might advance LIFR research?
Promising technological approaches include:
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Single-cell analysis: Single-cell RNA sequencing and proteomics to understand cell-specific LIFR signaling responses.
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Advanced imaging: Intravital microscopy to track LIFR-expressing cells in living tissues over time.
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CRISPR-based approaches: More sophisticated genetic engineering of LIFR domains to dissect specific signaling functions.
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Tissue-specific inducible models: More refined temporal and spatial control of LIFR expression or activity.
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Therapeutic ligand traps: Further engineering of soluble LIFR variants with enhanced affinity and selectivity for clinical applications .
What are promising therapeutic applications of LIFR research in mice?
Mouse models suggest several potential therapeutic applications:
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Cancer treatment: High-affinity soluble LIFR decoys that sequester LIF show promise for treating pancreatic and potentially other cancers with minimal toxicity in animal models .
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Cachexia management: PPARα agonists like fenofibrate can counteract LIF-induced cachexia by restoring lipid homeostasis, suggesting potential treatments for cancer cachexia .
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Developmental disorders: Given LIFR's role in placental development and CRH regulation, modulating LIFR signaling might address certain pregnancy complications or developmental disorders .
Product Science Overview
Leukemia Inhibitory Factor Receptor Alpha (LIFRα) is a critical component of the cytokine receptor family, specifically the interleukin-6 (IL-6) receptor family. This receptor plays a significant role in various biological processes, including cell growth, differentiation, and survival. The recombinant form of LIFRα, particularly from mouse models, has been extensively studied to understand its functions and applications in biomedical research.
LIFRα is a type I transmembrane protein with a molecular weight of approximately 190 kDa . It is also known as CD118 and is characterized by its ability to bind to the Leukemia Inhibitory Factor (LIF), a cytokine that influences cell growth by inhibiting differentiation . The receptor forms a heterodimer with the glycoprotein 130 (gp130) subunit, which is common to all IL-6 family members . This heterodimerization is crucial for the activation of various intracellular signaling pathways, including the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, the mitogen-activated protein kinase (MAPK) pathway, and the phosphoinositide 3-kinase (PI3K) pathway .
LIFRα is involved in numerous physiological processes. It is essential for embryonic development, neural differentiation, bone metabolism, and inflammation . In the context of stem cell research, LIFRα is particularly important for maintaining the pluripotency of embryonic stem cells. The receptor’s interaction with LIF prevents the differentiation of these cells, thereby promoting their self-renewal . This property is exploited in stem cell culture systems, where recombinant LIF is added to the culture media to maintain the undifferentiated state of stem cells .
The recombinant form of mouse LIFRα has been produced to facilitate various research applications. Recombinant proteins are typically generated using expression systems such as bacteria, yeast, or mammalian cells. These systems allow for the production of large quantities of the protein, which can then be purified and used in experimental studies . Recombinant LIFRα is used to study the receptor’s structure-function relationships, signaling mechanisms, and interactions with other proteins. Additionally, it serves as a valuable tool in drug discovery and development, particularly in identifying potential therapeutic targets for diseases involving aberrant LIFRα signaling .
Understanding the role of LIFRα in disease has significant clinical implications. Dysregulation of LIFRα signaling has been implicated in various pathological conditions, including cancer, neurodegenerative diseases, and inflammatory disorders . For instance, aberrant activation of the LIFRα/STAT3 pathway has been associated with tumor progression and resistance to apoptosis in certain cancers . Consequently, targeting LIFRα or its downstream signaling components presents a potential therapeutic strategy for these diseases.
