B6-hALB (HSA) Mice

Catalog Number: C001492

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

Strain Description

The ALB gene encodes albumin, which is mainly produced in the liver and is the most abundant protein in human plasma, accounting for 60% to 65% of total plasma protein. The proprotein encoded by ALB is processed to produce a functional protein, and the EPI-X4 peptide derived from this protein is an endogenous inhibitor of the CXCR4 chemokine receptor. Albumin plays a role in regulating plasma colloid osmotic pressure, helping to maintain blood circulation and isolating and transporting many metabolites within the body, especially insoluble hydrophobic metabolites ^[1]. Human Serum Albumin (HSA) is an important carrier protein involved in the transport of a variety of endogenous molecules, including hormones, fatty acids, and metabolic products, as well as exogenous drugs. As a natural carrier protein, HSA has multiple ligand binding sites and a plasma half-life of up to 19 days, making it a highly promising drug carrier. Several HSA-based drug delivery systems have been approved for clinical trials ^[2-3]. In addition, albumin is also the main transporter of zinc, calcium, and magnesium in plasma, binding approximately 80% of all plasma zinc and approximately 45% of circulating calcium and magnesium, with an affinity ranking of zinc > calcium > magnesium ^[4]. Diseases associated with the ALB gene include hyperthyroxinemia, familial serum albumin abnormality, and analbuminemia ^[5].

This strain is a humanized mouse model of the Alb gene, obtained by in situ replacement of the entire mouse Alb gene sequence, including the UTR region, with the human ALB gene sequence. This model can be used for the development of ALB-targeted drugs, as well as for the research and development of drugs using HSA as a carrier, and for in vivo pharmacodynamics and pharmacokinetics studies, including albumin-drug conjugates or albumin-binding prodrugs.

Strain Strategy

Figure 1. Schematic representation of the gene editing strategy for generating B6-hALB (HSA) mice. Both the mouse Alb gene and the human ALB gene contain 15 exons. The mouse Alb gene sequence (approximately 10kb upstream of Exon 1 to approximately 500bp downstream of Exon 15) was replaced with the human ALB gene sequence (approximately 100kb upstream of Exon 1 to approximately 1kb downstream of Exon 15) using embryonic stem cell (ES) gene editing technology.

Validation Data

1. Detection of human ALB gene expression in liver

Figure 2. Detection of human ALB gene expression in liver tissue of C57BL/6N wild-type and B6-hALB (HSA) mice. Quantitative PCR analysis revealed the expression of the human ALB gene in the liver of B6-hALB (HSA) mice, but not in wild-type mice.

 

2. Detection of ALB protein expression in serum

Figure 3. Detection of the ALB protein in the serum of C57BL/6N wild-type and B6-hALB (HSA) mice. Elisa analysis of ALB protein expression revealed the significant expression of human ALB protein in the serum of B6-hALB (HSA) mice (n=5) compared to C57BL/6N wild-type mice (n=5).

Reference

[1] Caraceni P, Tufoni M, Bonavita ME. Clinical use of albumin. Blood Transfus. 2013 Sep;11 Suppl 4(Suppl 4):s18-25.

[2] Lei C, Liu XR, Chen QB, Li Y, Zhou JL, Zhou LY, Zou T. Hyaluronic acid and albumin based nanoparticles for drug delivery. J Control Release. 2021 Mar 10;331:416-433.

[3] Tiwari R, Sethiya NK, Gulbake AS, Mehra NK, Murty USN, Gulbake A. A review on albumin as a biomaterial for ocular drug delivery. Int J Biol Macromol. 2021 Nov 30;191:591-599.

[4] Konopka K, Neilands JB. Effect of serum albumin on siderophore-mediated utilization of transferrin iron. Biochemistry. 1984 May 8;23(10):2122-7.

[5] Arques S. Human serum albumin in cardiovascular diseases. Eur J Intern Med. 2018 Jun;52:8-12.