PXB-mouse®

Increased translational potential through the use of a chimeric mouse with a humanized liver

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What is a humanized liver animal model?

Humanized liver mouse models are generated on suitable transgenic backgrounds that allow for the ablation of the endogenous mouse hepatocyte and accept the engraftment of xenotransplanted human hepatocytes to fully repopulate as a functional human liver. These preclinical animal models increase the translational prediction of human results early on in the drug discovery and development process.

A major challenge faced in drug discovery and early development studies is the discrepancy between mouse and human data. Mice, and other laboratory animals, are often poor predictors of human drug responses, including metabolism, pharmacokinetics, efficacy, and hepatotoxicity of small molecule drugs, biologics, adeno-associated viruses and other gene therapy delivery systems. Targeting human specific infections, like viral hepatitis, also presents unique challenges in commonly used pre-clinical animal species.

That’s why we created the PXB-mouse®, a cDNA-uPA/SCID mouse transplanted and engrafted with primary human hepatocytes that can better anticipate human outcomes for your therapeutics. Characterized and optimized for nearly two decades, our high-quality PXB-mouse® provides you with robust insights into how your drug performs in a human liver environment.

Predict human outcomes using chimeric PXB-mice with humanized livers, that have:

  • Up to 95% human hepatocyte engraftment
  • Normal human liver histology and function
  • Human-specific metabolism and excretion pathways
  • Expression of human genes, mRNA, and proteins
  • Human-like lipid profiles
  • Production of human albumin and human-like biliary excretion
  • A wide range of research applications

 

  • Complete project management process to cover an entire research plan, not only one project.
  • Interim Reporting throughout the in-life phase.
  • Various dosing routes, quantitative small volume blood collection methods, and technical
    procedures such as gallbladder cannulation are available upon request.
  • In-house HBV assays & a proprietary h-ALT1 assay streamline studies and add value for clients.
  • Strict animal selection criteria to ensure highest quality animals with similar body weight, age, and replacement index are always selected for studies and supply shipments.
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Study services with PXB-mice

PhoenixBio provides contract research services for Pharmaceutical & Agrochemical industry leaders using PXB-mice for the assessment of human outcomes.

Our unique approach is built on being a supportive partner, providing end-to-end solutions that are tailored to suit your needs, while ensuring full confidence in the study approach and data generated.

With our dedicated study team offering decades of experience, we provide project-specific long-term study services that are unique to PhoenixBio and the PXB-mouse® model.

Why choose the PXB-mouse®?

High and Stable Liver Humanization

PXB-mice have up to 95% human hepatocyte engraftment in the liver, and express stable blood levels of human albumin, a biomarker of humanization, over their life span. That means you can rely on high quality, stable human physiology in the convenience of a mouse.

 

PXB-mice are ready to use for supply shipment or study services as early as 12-weeks of age when humanization of the liver meets our criteria.

Humanized Liver PHH Engraftment

Production Quality Control & Strict Animal Selection Criteria

Prior to commercial production of any new donors, PhoenixBio validates engraftment of human hepatocytes by immunohistochemical analysis of the PXB-mouse liver. Upon validation of liver humanization, we build a correlation of the dimensional replacement of the liver (via immunohistochemistry analysis) to the blood h-Alb (via a latex agglutination immunonephelometry test). 

Every PXB-mouse provided is selected with narrow ranges of age, body weight, and most importantly, the level of human hepatocyte engraftment in the liver. 

Selection Criteria

Criteria Averages*
Replacement Index 85 ~ 90%

Body weight

19 - 20 g

Age

From 12 weeks

* Average ranges of PXB-mice used for study services or supply shipments to clients

Recreation of Human Liver Physiology

The PXB-mouse liver accurately represents the normal physiology of the human liver, even at the ultrastructural level. Human hepatocytes are engrafted uniformly throughout all of the liver lobes. Even further, the PXB-mouse liver has appropriate patterns of zone-dependent expression of representative cytochrome P450 enzymes and arginase I, fully demonstrating the formation of hepatic zonation. Human bile secretion machinery is also established in the humanized liver chimeric mouse model.

Both structural & functional characteristics of the human liver are established in PXB-mice and key to the quality of translational outcomes.

HUMAN HEPATOCYTE STAINING

Metabolic enzymes

CYP2E1

UGT2B7

CYP3A4

UGT1A1

CYP2C9

CYP1A2

CYP2C8

CYP2A6

CYP4A11

CYP2D6

CYP2C19

CYP3A5

CYP2B6

CYP3A7

Transporters

OCT1

BSEP

MDR3

OAT2

MDR1

MRP2

MRP6

NTCP

ENT1

MATE1

OATP2B1

OATP1B3

OATP1B1

γ-GPT

Human gene and protein expression in the PXB-mouse®

PXB-mice express a wide range of human liver genes, making them ideal models to test human gene therapies.

PXB-mouse® hepatocytes resemble human hepatocytes and human livers

Liver gene expression

*82% of the genes investigated were expressed at similar levels in PXB-mouse® hepatocytes (c-heps) and human liver hepatocytes (h-heps)

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High quality, high production capacity

Plan your large-scale animal experiments for drug discovery and development projects with our stable production capacity of over 100 PXB-mice every week. Rest assured that we can accommodate your requirements for a reliable and large supply of PXB-mice.

Our PXB-mouse® model is best utilized at stages of your project when you need confidence in the human metabolism, efficacy, and toxicity of your lead therapeutics prior to clinical trials.

Ongoing research using PXB-mice

Publications

PXB-mice have increased the translational potential of these research studies

Resources hub
research applications

Research applications of the PXB-mouse®

Maximise the quality of your research studies with PXB-mice in a wide range of drug discovery and early development projects.

Our proven track record has driven the publication of hundreds of research publications in the last decade.

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Get in Touch

Contact us to find out how the PhoenixBio team could help your drug discovery and development projects today.

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