The path to a new drug is fraught with challenges, but for rare diseases, a fundamental hurdle often emerges at the very beginning: the lack of high-fidelity animal models. Without a reliable model that accurately mimics human pathology, validating therapeutic concepts and securing funding becomes a monumental task.
At Cyagen, we believe that empowering researchers with the right tools is the first step toward solving these complex puzzles. Our mission is not just to provide models, but to bridge the critical gap between basic research and clinical translation. Through our Rare Disease Data Center (RDDC), we aim to be a central resource for the scientific community, offering the data and models needed to accelerate the journey from discovery to clinic.
Copper is an essential trace element for many biological processes, but maintaining its normal physiological level is crucial [2]. The body’s copper metabolism is a complex process involving the absorption, utilization, storage, and excretion of this element [2]. A key player in this process is the ATP7B protein, a copper-transporting P-type ATPase primarily expressed on the Golgi apparatus membrane of liver cells [5]. Its core function is to use energy from ATP hydrolysis to transport copper ions (Cu+) from the cytoplasm into the Golgi, where it binds with ceruloplasmin before being excreted [5]. This dynamic process is vital for preventing the toxic accumulation of copper [5].
Wilson's Disease (WD), also known as hepatolenticular degeneration (HLD), is an autosomal recessive genetic disorder caused by a defect in the ATP7B gene, leading to copper metabolism dysfunction [2, 8]. Patients with WD cannot effectively excrete excess copper, which then accumulates abnormally in organs like the liver and brain, causing a range of severe symptoms including cirrhosis, neurological disorders, and organ dysfunction [2, 8, 10].
Figure 3. Illustration of Wilson’s Disease Symptoms
To meet the scientific community's need for a high-fidelity model, we developed the B6-hATP7B*H1069Q Humanized Mouse Model [13]. This model, built on our HUGO-GT Humanized Mouse platform, is a testament to our commitment to scientific precision. It's engineered to carry the human ATP7B gene with the p.H1069Q mutation, accurately reproducing the ERAD-induced protein degradation seen in human patients [15, 19, 21].
| Product Name | Catalog Number | Strain Name | Type |
|---|---|---|---|
| B6-hATP7B | I001130 | C57BL/6NCya-Atp7btm1(hATP7B)/Cya | ATP7B Humanized(Wild-type) |
| B6-hATP7B*H1069Q | C001610 | C57BL/6NCya-Atp7btm2(hATP7B*H1067Q)/Cya | ATP7B Humanized (with H1069Q mutation) |
| Atp7b KO | C001267 | C57BL/6NCya-Atp7bem1(Cyagen)/Cya | Atp7b Gene Knockout |
gene in the liver and lungs, with no expression of the mouse Atp7b gene [16]. This ensures a human-specific context for research.
Protein Expression: While both models show similar human ATP7B gene expression levels, the B6-hATP7B*H1069Q model shows significantly lower ATP7B protein levels due to the ERAD effect [19]. This precisely mirrors the pathology observed in human patients with the H1069Q mutation [19, 21].
[1] Ling W, Li S, Zhu Y, Wang X, Jiang D, Kang B. Inducers of Autophagy and Cell Death: Focus on Copper Metabolism. Ecotoxicol Environ Saf. 2025 Jan 15;290:117725.
[2] Zhou Y, Zhang L. The interplay between copper metabolism and microbes: in perspective of host copper-dependent ATPases ATP7A/B. Front Cell Infect Microbiol. 2023 Nov 30;13:1267931.
[3] La Fontaine S, Mercer JF. Trafficking of the copper-ATPases, ATP7A and ATP7B: role in copper homeostasis. Arch Biochem Biophys. 2007;463(2):149-167.
[4] Cater MA, et al. ATP7B mediates vesicular sequestration of copper: insight into biliary copper excretion. Gastroenterology. 2006;130(2):493-506.
[5] Banci L, et al. Cellular copper distribution: a mechanistic systems biology approach. Cell Mol Life Sci. 2010;67(15):2563-2589.
[6] Lutsenko S, et al. Biochemical basis of regulation of human copper-transporting ATPases. Arch Biochem Biophys. 2007;463(2):134-148.
[7] Bull PC, et al. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet. 1993;5(4):327-337.
[8] Tanzi RE, et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet. 1993;5(4):344-350.
[9] Ferenci P. Pathophysiology and clinical features of Wilson disease. Metab Brain Dis. 2004;19(3-4):229-239.
[10] Członkowska A, Litwin T, Dusek P, Ferenci P, Lutsenko S, Medici V, Rybakowski JK, Weiss KH, Schilsky ML. Wilson disease. Nat Rev Dis Primers. 2018 Sep 6;4(1):21.
[11] Ala A, et al. Wilson's disease. Lancet. 2007;369(9559):397-408.
[12] Huster D, et al. Diverse functional properties of Wilson disease ATP7B variants. Gastroenterology. 2012;142(4):947-956.e5.
[13] Lutsenko S, et al. Biochemical basis of regulation of human copper-transporting ATPases. Arch Biochem Biophys. 2007;463(2):134-148.
[14] Huster D, et al. Diverse functional properties of Wilson disease ATP7B variants. Gastroenterology. 2012;142(4):947-956.e5.
[15] Parisi S, Polishchuk EV, Allocca S, Ciano M, Musto A, Gallo M, Perone L, Ranucci G, Iorio R, Polishchuk RS, Bonatti S. Characterization of the most frequent ATP7B mutation causing Wilson disease in hepatocytes from patient induced pluripotent stem cells. Sci Rep. 2018 Apr 19;8(1):6247.
[16] Prime Medicine. (2024). AASLD WD Talk (Version 3): Advances in prime editing enable in vivo therapeutic correction of the ATP7B p.H1069Q and p.R778L mutations causing Wilson’s disease. Retrieved from https://primemedicine.com/wp-content/uploads/2024/12/2024-11-18-AASLD-WD-Talk-v3_Final_PDF.pdf
