Atp7b KO Mice

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Product Number：C001267

Genetic Background：C57BL/6NCya

Reproduction：Homozygous male x Heterozygous female


Strain Description

The ATP7B gene encodes a copper-transporting ATPase β-peptide that is a member of the P-type cation-transporting ATPase family, which uses the energy stored in adenosine triphosphate (ATP) molecules to transport metals into and out of cells. The ATP7B protein consists of multiple transmembrane structural domains, an ATPase consensus sequence, a hinge structural domain, and a phosphorylation site, as well as at least two putative copper-binding sites [1]. This protein is found mainly in the liver and to a lesser extent in the kidney and brain, and functions as a copper-transporting ATPase that plays a role in transporting copper from the liver to other parts of the body. Copper is an important component of certain enzymes that maintain normal cellular function, and the ATP7B protein is important for the removal of excess copper from the body. Mutations in this gene are associated with Wilson disease (WD), which is characterized by the accumulation of copper to toxic levels that damage tissues and organs such as the liver and brain as the removal of excess copper from the body is compromised with the absence of the functional ATP7B protein [2-4].

This strain is an Atp7b deletion mouse model, which uses gene editing technology to knock out Atp7b, the homolog of the human ATP7B gene in mice that lack the expression of ATP7B protein and can be used in the study of disorders related to copper metabolisms such as Wilson's disease, acute liver failure, and steatohepatitis. The heterozygous Atp7b KO mice are viable and fertile, and homozygous mice have a reduced life expectancy.

 

The Atp7b gene is located on mouse chromosome 8, and Exon 2~20 of this gene was deleted.

● Copper Metabolism Research;

● Wilson’s Disease Research;

● Acute Liver Failure Research;

● Steatohepatitis Research;

● Other Research Related to Copper Metabolism Disorders.

1. Hepatic Atp7b mRNA expression

Figure 1. Detection of Atp7b mRNA expression in the livers of Atp7b KO mice and wild-type mice. Atp7b mRNA expression was almost absent in the liver of Atp7b KO mice (Model) compared to the wild type (Control).

2. Hepatic ATP7B protein expression

Figure 2. Detection of Atp7b protein expression in the livers of Atp7b KO and wild-type (WT) mice. ATP7B protein expression was absent in the liver of Atp7b KO mice (KO) compared to wild-type controls.

3. Liver and kidney function tests

Figure 3. Liver and kidney function tests in 8-week-old Atp7b KO and wild-type mice. Compared to the wild-type group (Control), Atp7b KO mice (Atp7b-/-) showed significantly elevated levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the liver, and creatinine (CREA-S) and uric acid (UA) in the kidney, suggesting hepatic and renal metabolic abnormalities.

4. H&E staining of liver tissue

Figure 4. H&E staining of liver tissues from 8-week-old Atp7b KO and wild-type (WT) mice. Hematoxylin and eosin (H&E) staining revealed that Atp7b KO mice had enlarged nuclei and disrupted cell membranes in the liver, compared to wild-type mice.

5. Summary

The Atp7b KO mice were generated by targeted disruption of the Atp7b gene. Validation studies showed that the loss of Atp7b gene expression in Atp7b KO mice resulted in the loss of Atp7b mRNA and ATP7B protein expression, leading to hepatic and renal functional abnormalities, as well as hepatic histopathological abnormalities. These findings are consistent with the clinical disease phenotype caused by ATP7B deficiency, suggesting that Atp7b KO mice are a valuable model for the study of copper metabolism disorders such as Wilson's disease, acute liver failure, and non-alcoholic fatty liver disease.

References

[1] Cater MA, Forbes J, La Fontaine S, Cox D, Mercer JF. Intracellular trafficking of the human Wilson protein: the role of the six N-terminal metal-binding sites. Biochem J. 2004 Jun 15;380(Pt 3):805-13.
[2] Panagiotakaki E, Tzetis M, Manolaki N, Loudianos G, Papatheodorou A, Manesis E, Nousia-Arvanitakis S, Syriopoulou V, Kanavakis E. Genotype-phenotype correlations for a wide spectrum of mutations in the Wilson disease gene (ATP7B). Am J Med Genet A. 2004 Dec 1;131(2):168-73.
[3] Ferenci P. Regional distribution of mutations of the ATP7B gene in patients with Wilson disease: impact on genetic testing. Hum Genet. 2006 Sep;120(2):151-9.
[4] Fatemi N, Sarkar B. Molecular mechanism of copper transport in Wilson disease. Environ Health Perspect. 2002 Oct;110 Suppl 5(Suppl 5):695-8.