Knockout Mouse Catalog | Cyagen APAC

Humanized PK/PD Mouse

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Model Description

Double Humanized Neonatal Fc Receptor (FcRn)/Serum Albumin (SA) - AlbuMusTM Model

Improving the pharmacokinetic properties of therapeutic proteins has become a major challenge in the development of advanced biologics over the past decade.

By fusing or conjugating therapeutic protein drugs to human albumin, to enhance their half-life from minutes to hours, and even to days. The reasons for the prolonged half-life of albumin-linked drugs are:

  • The high-affinity interaction between human albumin and neonatal Fc receptor (FcRn) can protect protein drug molecules from being cleared by the kidney and finally transport into the cell.
  • There are huge differences in the SA/FcRn interaction between mouse and human, which limits the use of mice as a preclinical model to detect the pharmacokinetics (PK) of protein drugs that bind to albumin.

The humanized SA/FcRn mouse for preclinical drug metabolism prediction can more accurately predict the half-life of candidate drugs.

Strain Background: C57BL/6N

Model Description:
The expression of hSA in previously established albumin humanized models did not conform to the normal physiological level and expression pattern. Through in-depth analysis of the maturation process of albumin complex and FcRn expression and regulation, a double humanized SA/FcRn model was established - the physiological level of hSA and the expression pattern of hFcRn in this model accord with the normal physiological level.

  • HSA and hFcRn are controlled by their respective endogenous mouse promoters, replacing the corresponding gene expression in mice.
  • AlbuMusTM express human albumin at a physiological level (within the normal range of 1.5–6 g/dL), and display normal blood chemistry.
  • The experimental data of blood chemistry of AlbuMusTM mouse is silmilar to that of the wildtype.
  • AlbuMusTM, double humanized FcRn/albumin mouse model maintains an normal autologous receptor/ligand interaction required for albumin-linked drugs and biologics (their half-life correlates with data obtained in non-human primates).
  • AlbuMusTM model can mimic the physiological status in humans,therefore it is widely used in the development of biologics that related to SA reversible binding proteins and conventional drugs.
  • The humanized FcRn/albumin mouse model is an uniquel tool for studying the PK/PD of albumin-linked drugs.

 

Model Validation

Graph 1. Expression of hFcRn is physiological. Upper panel: hFcRn expression (analyzed by qPCR) in duodenum (Du), jejunum (Je), ileum (iLe), large intestine (Li), liver (H), kidney (K), and lung (Lu) Lower panel: Immunohistochemical staining for hFcRn in HSA/FcRn humanized (large image) and wild-type (small insert) mice. No cross reactivity to mouse FcRn was seen in the wild-type mice (small insert).

 

Model Validation

Graph 2. Half-life of drug conjugated to human albumin is extended in our double humanized model. (Left) Albumin-bound drug 1: low affinity for hFcRn; (Right) Albumin-bound drug 2: high affinity for hFcRn

 

Model Validation

Graph 3. Half–life of a drug (Exenatide) conjugated with Veltis® is doubled in AlbuMusTM mice compared to wild type mice. In AlbuMusTM mice, the half–life of the Exenatide conjugated with HB-Veltis® is doubled compared to the one coupled with first generation technology (Veltis® NS). Therefore, the extended half-life of the compound is due to Veltis® high affinity for human FcRn.

 

*For more validation data please contact us.

Category Strain Name Background Order Amount
(head)
List Price
(USD/head)
Order Now
Humanized PK/PD Mice hFcRn+hAlbumin C57BL/6N 1~50 $619
51-199 $559
>200 $509

Price Availability

  • Sex: Female
  • Age: 3 to 8 weeks
  • Customers in Asia Pacific region, excluding Japan.

*If you would like to order male mice, Please contact us.

Digital Resources:

Humanized PK/PD Mouse
(poster)
Download
Mouse Models for
Drug Screening & Assessment
(brochure)
Download
Cyagen Animal Models
Catalog - 2021
(brochure)
Download

Viuff D, Antunes F, Evans L, et al. Generation of a double transgenic humanized neonatal Fc receptor (FcRn)/albumin mouse to study the pharmacokinetics of albumin-linked drugs. Journal of Controlled Release, 2016: 22-30.

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With more than 15 years’ experience in genetic engineering, Cyagen offers a complete range of products and services to support the advancement of human disease research. Cyagen is committed to enabling the development of therapeutics for human diseases by providing one-stop research solutions – from custom rodent model generation and breeding, through therapeutic viral packaging and injection, and phenotype analysis to study disease mechanisms, target validation, drug screening and more.

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