huIL1B/huTFRC Mouse
Product Name
huIL1B/huTFRC Mouse
Product ID
C002028
Strain Name
C57BL/6NCya-Il1btm1(hIL1B)Tfrctm2(hTFRC)/Cya
Backgroud
C57BL/6NCya
Status
When using this mouse strain in a publication, please cite “huIL1B/huTFRC Mouse (Catalog C002028) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
IL1B & TFRC
Gene Alias
IL-1, IL1F2, IL1beta, IL1-BETA, T9, TR, TFR, p90, CD71, TFR1, TRFR, IMD46
NCBI ID
Chromosome
Chr 2 (Human), Chr 3 (Human)
Datasheet
Strain Description
Interleukin-1β (IL-1β), encoded by the IL1B gene, is a cytokine with potent pro-inflammatory activity that plays a central role in inflammatory responses and innate immune regulation. It induces the release of various inflammatory mediators and activates immune cells, participating in the regulation of biological processes such as cell proliferation, differentiation, apoptosis, and febrile responses [1-2]. Studies have shown that abnormal expression or activity of IL-1β is closely associated with various pathological processes, including cryopyrin-associated periodic syndromes (CAPS), gout, rheumatoid arthritis (RA), recurrent pericarditis, type 2 diabetes mellitus (T2DM), and other inflammatory and autoimmune diseases, while also playing an important role in the pathogenesis of multiple malignancies and neurodegenerative diseases [3-4]. Transferrin receptor 1 (TFRC) is a transmembrane protein widely expressed across diverse cells and tissues, playing a critical role in iron transport and the maintenance of iron homeostasis. It is highly expressed on brain capillary endothelial cells, making it a vital target for drug delivery across the blood-brain barrier (BBB) [5-6]. In recent years, TFRC-mediated receptor-mediated transcytosis (RMT) has become a key strategy for improving the delivery efficiency of therapeutic antibodies and other macromolecular drugs across the BBB. In neuroinflammatory diseases such as multiple sclerosis (MS), IL-1β can promote microglial activation, induce pathogenic Th17 cell responses, increase BBB permeability, and facilitate the recruitment of inflammatory cells, thereby driving central nervous system inflammation and demyelinating injury [7-8].
The huIL1B/huTFRC mouse is a dual-gene humanized model obtained by crossing the huIL1B mouse (Catalog No.: C001791) with the huTFRC mouse (Catalog No.: C001860). Co-expressing human IL1B and TFRC targets, this model can be utilized for the screening, pharmacodynamic evaluation, safety assessment, and mechanism-of-action studies of IL1B/TFRC-targeted drugs. Meanwhile, it is suitable for evaluating the trans-BBB delivery capacity of therapeutic agents, providing an ideal preclinical research platform for the development of innovative therapies for neuroinflammatory diseases, such as multiple sclerosis (MS).
Reference
Lopez-Castejon G, Brough D. Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev. 2011 Aug;22(4):189-95.
Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018 Jan;281(1):8-27.
Baker KJ, Houston A, Brint E. IL-1 Family Members in Cancer; Two Sides to Every Story. Front Immunol. 2019 Jun 7;10:1197.
Tylutka A, Walas Ł, Zembron-Lacny A. Level of IL-6, TNF, and IL-1β and age-related diseases: a systematic review and meta-analysis. Front Immunol. 2024 Mar 1;15:1330386.
Candelaria PV, Leoh LS, Penichet ML, Daniels-Wells TR. Antibodies Targeting the Transferrin Receptor 1 (TfR1) as Direct Anti-cancer Agents. Front Immunol. 2021 Mar 17;12:607692.
Xu W, Barrientos T, Mao L, Rockman HA, Sauve AA, Andrews NC. Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart. Cell Rep. 2015 Oct 20;13(3):533-545.
Mendiola AS, Cardona AE. The IL-1β phenomena in neuroinflammatory diseases. J Neural Transm (Vienna). 2018 May;125(5):781-795.
Lai S, Wu X, Liu Y, Liu B, Wu H, Ma K. Interaction between Th17 and central nervous system in multiple sclerosis. Brain Behav Immun Health. 2024 Dec 24;43:100928.
Strain Strategy
The huIL1B/huTFRC mouse is a dual-gene humanized model obtained by crossing huIL1B mice (Catalog No.: C001791) with huTFRC mice (Catalog No.: C001860).
Figure 1. Gene editing strategy of huIL1B mice. The sequences from the start codon to the stop codon of the endogenous mouse Il1b gene will be replaced with the sequences from the start codon to the stop codon of the human IL1B gene. The function of the mouse Il1bos gene will be affected.
Figure 2. Gene editing strategy of huTFRC mice. The mouse Tfrc endogenous extracellular domain was replaced with the human TFRC extracellular domain. The murine cytoplasmic and helical regions were kept.
Application Area
Screening, pharmacodynamic evaluation, safety assessment and mechanism of action research of IL1B/TFRC-targeted drugs;
Evaluate the delivery ability of therapeutic drugs across the blood-brain barrier (BBB) and develop innovative therapies for neuroinflammatory diseases, such as multiple sclerosis (MS).
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