B6-hTFRC/Ube3a KO Mouse
Product Name
B6-hTFRC/Ube3a KO Mouse
Product ID
C001737
Strain Name
C57BL/6NCya-Tfrctm1(hTFRC)Ube3aem1/Cya
Backgroud
C57BL/6NCya
When using this mouse strain in a publication, please cite “B6-hTFRC/Ube3a KO Mouse (Catalog C001737) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Alias
Hpve6a, 4732496B02, 5830462N02Rik, A130086L21Rik, T9, TR, TFR, p90, CD71, TFR1, TRFR, IMD46
Chromosome
Chr 7, Chr 3
MGI ID
Datasheet
Strain Description
The UBE3A gene encodes ubiquitin-protein ligase E3A, a critical enzyme in the ubiquitin-proteasome degradation system responsible for catalyzing substrate ubiquitination and regulating proteasomal clearance. This process is indispensable for maintaining proteostasis, particularly in neurons, where UBE3A governs synaptic plasticity, neural signaling, and neurodevelopment by modulating the levels of specific substrates. As an imprinted gene, UBE3A exhibits parent-of-origin-specific expression in brain neurons. The paternal allele is epigenetically silenced via cis-acting repression by a long noncoding antisense transcript (UBE3A-ATS) [1]. Consequently, only the maternal UBE3A allele is functionally active in neuronal populations. Loss of maternal UBE3A function disrupts ubiquitin-mediated proteolysis, leading to aberrant accumulation of neurodevelopmental regulators and subsequent dysregulation of synaptic maturation and circuit formation. These molecular deficits underlie the pathogenesis of Angelman syndrome (AS), a severe neurogenetic disorder. Patients with Angelman Syndrome commonly exhibit severe motor and intellectual developmental delays, ataxia, hypotonia, epilepsy, speech impairment, and distinctive facial features [2].
The Transferrin receptor (TFRC) gene encodes Transferrin Receptor 1 (TFR1), a protein that is expressed at low levels in most normal cells but shows increased expression in highly proliferative cells, such as basal epidermal cells, intestinal epithelium, and certain activated immune cells. Brain capillary endothelial cells, which constitute the blood-brain barrier (BBB), also express this receptor at high levels [3]. TFR1 plays a critical role in maintaining iron metabolism and homeostasis by facilitating receptor-mediated endocytosis of iron-bound transferrin (Tf) via Tf cycling, thereby promoting iron uptake [4]. Cellular iron deficiency can lead to apoptosis, while cellular transformation requires substantial iron to sustain proliferation, with iron overload contributing to tumor progression. The high expression of TFR1 in many tumors makes it a potential tumor marker, offering a target for therapies to inhibit tumor growth and metastasis [3]. Moreover, TFR1 is implicated in anemia and iron metabolism disorders. Studies have shown that elevated TFR1 expression in cardiomyocytes is associated with exacerbated inflammation in myocarditis patients [5].
The B6-hTFRC/Ube3a KO mice are generated by crossing B6-hTFRC(CDS) mice with Ube3a KO mice. These mice can be used for studying the pathogenesis of Angelman syndrome (AS), developing related therapeutic approaches, and conducting preclinical research on TFRC-targeted drugs.
Reference
Krzeski JC, Judson MC, Philpot BD. Neuronal UBE3A substrates hold therapeutic potential for Angelman syndrome. Curr Opin Neurobiol. 2024 Oct;88:102899.
Buiting K, Williams C, Horsthemke B. Angelman syndrome - insights into a rare neurogenetic disorder. Nat Rev Neurol. 2016 Oct;12(10):584-93.
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.
Kobak KA, Franczuk P, Schubert J, Dzięgała M, Kasztura M, Tkaczyszyn M, Drozd M, Kosiorek A, Kiczak L, Bania J, Ponikowski P, Jankowska EA. Primary Human Cardiomyocytes and Cardiofibroblasts Treated with Sera from Myocarditis Patients Exhibit an Increased Iron Demand and Complex Changes in the Gene Expression. Cells. 2021 Apr 6;10(4):818.
Strain Strategy
Figure 1. Diagram of the gene editing strategy for the generation of B6-hTFRC(CDS) mice. TurboKnockout targeting technology was used to replace part of exon 2 of the mouse Tfrc gene with a human TFRC chimeric cDNA WPRE-BGH pA cassette. Gene-editing techniques were employed to knock out exons 10-13 of the mouse Tfrc gene.
Figure 2. Gene editing strategy of Ube3a KO mice. The Ube3a gene in mice consists of 13 exons, with the start codon located in exon 3 and the stop codon in exon 13. This strain was created by knocking out the exon 6 using gene editing technology.
Application Area
Research on the pathogenic mechanisms and therapeutic drugs of Angelman Syndrome (AS);
Other neurological system studies.
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