Corporate Banner
Satellite Banner
Biologics & Bioprocessing
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

‘Humanized’ Mice Developed at Oregon Health & Science University

Published: Wednesday, September 12, 2012
Last Updated: Wednesday, September 12, 2012
Bookmark and Share
Transgenic mouse technology contributes to research discoveries around the globe, enables malaria research breakthrough.

A novel human liver-chimeric mouse model developed at Oregon Health & Science University and Yecuris Corporation has made possible a research breakthrough at Seattle Biomedical Research Institute that will greatly accelerate studies of the most lethal forms of human malaria.

The study findings are published online in the Journal of Clinical Investigation. Study photos were selected to appear in “Scientific Show Stoppers” on the JCI blog.

Plasmodium falciparum, one of two human-specific malaria parasites, is a global health crisis, causing more than 216 million new infections annually and resulting in an estimated 655,000 deaths, according to the World Health Organization.

Sporozoites, the infectious form of the parasite, are spread to people through the bites of infected mosquitos and multiply in the human liver during the initial stages of infection. There, they undergo liver stage development, culminating in the formation and release of tens of thousands of merozoites, the parasitic phase of development that infects red blood cells.

Until now, there have been few data on human malaria liver stage biology due to the lack of a viable small animal model and because liver stage P. falciparum does not grow well in a dish. Consequently, most research and therapeutics to date have targeted the human blood stage of P. falciparum’s development because it replicates well in culture.

The liver-to-blood stage of P. falciparum is the focus of this research because the parasite is virtually harmless, causing no disease symptoms, prior to its transition to the blood stage.

In this study, researchers at Seattle Biomedical Research Institute, Yecuris Corporation, Oregon Health & Science University and The Rockefeller University have demonstrated that a complete liver-to-blood stage infection of P. falciparum is possible using a unique immunocompromised mouse model engrafted with human liver-chimeric cells.

The mouse model, termed the FRGTM KO mouse, was developed by paper co-author and internationally accomplished stem cell researcher Markus Grompe, M.D., in the Papé Family Pediatric Research Institute, a research arm of Oregon Health & Science University Doernbecher Children’s Hospital.

In 2007 the technology was licensed to Yecuris Corporation, a biotechnology company that now produces the model and human hepatocytes on a commercial scale. As a result of this work, the FRGTM KO mouse now will be used to study new drug interventions, parasite attenuation and innate immune responses to P. falciparum liver stage infection.

The scientists also report that through the infection of the FRGTM KO mouse model, they were able to observe a previously unknown expression of proteins in liver stage development in humans that may be exploited for intervention. Equally important, they say, the FRGTM KO mouse could well provide unique opportunities for the study of another severe form of human malaria, Plasmodium vivax.

“These breakthroughs are remarkable and highlight OHSU and Yecuris’ contributions to local biotechnology and research breakthroughs globally. The next generation mouse model we’re developing will have a human immune system that will allow us to test not just drugs, but vaccines, which has never been done for parasitic diseases,” said Grompe, Ray Hickey Chair and Director of the Papé Family Pediatric Research Institute, OHSU Doernbecher Children’s Hospital; and professor of pediatrics, and molecular and medical genetics, OHSU School of Medicine.

Grompe founded Yecuris Corporation in 2007 and is a shareholder. John Bial, who joined Yecuris in 2009, is president and chief executive officer.

“The extensive collaborative relationships and risk-taking involved in planning and executing this research is a testament to the tireless dedication of these teams to solving one of the globe's oldest killers. It also highlights how private and public funding can come together effectively to address critical challenges in global health,” said Bial.

“This first demonstration of the newly developed dual humanized FRGTM KO system is a good introduction to the kinds of translational medicine benefits that we can expect to see from these technologies. We anticipate that the next frontier for these systems will be as platforms for human vaccine development and validation, which may very likely first be tested in the area of malaria,” Bial explained.

Investigators who contributed to this work include: Stefan Kappe, Ashley Vaughan, Sebastian Mikolajczak, Alexis Kaushansky, Nelly Camargo, Seattle Biomedical Research Institute; Elizabeth Wilson, John Bial, Yecuris Corporation; Markus Grompe, Papé Family Pediatric Research Institute, Oregon Stem Cell Center, Oregon Health & Science University, Doernbecher Children’s Hospital; and Alexander Ploss, Center for the Study of Hepatitis C, The Rockefeller University.

Today’s JCI study, “Complete Plasmodium falciparum liver stage development in liver-chimeric mice,” was funded by grants to the Seattle Biomedical Research Institute from the Bill and Melinda Gates Foundation (OPP1016829) and the Department of Defense (W81XWH?11?2?0184).

The Oregon Health & Science University research leading to the development of the FRGTM KO mouse was funded by the National Institutes of Health and the The Oregon Opportunity fund.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,100+ scientific posters on ePosters
  • More than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
Developing a More Precise Seasonal Flu Vaccine
During the 2014-15 flu season, the poor match between the virus used to make the world’s vaccine stocks and the circulating seasonal virus yielded a vaccine that was less than 20 percent effective.
Fighting Cancer with Borrowed Immunity
A new step in cancer immunotherapy: researchers from the Netherlands Cancer Institute and University of Oslo/Oslo University Hospital show that even if one's own immune cells cannot recognize and fight their tumors, someone else's immune cells might.
Modified Microalgae Converts Sunlight into Valuable Medicine
A special type of microalgae can soon produce valuable chemicals such as cancer treatment drugs and much more just by harnessing energy from the sun.
Immune Cells Remember Their First Meal
Scientists at the University of Bristol have identified the trigger for immune cells' inflammatory response – a discovery that may pave the way for new treatments for many human diseases.
Paper Filter Can Remove Viruses from Water
A new paper filter can purify water from viruses, even the most difficult and contagious.
Large-scale HIV Vaccine Trial to Launch in South Africa
NIH-funded study will test safety, efficacy of vaccine regimen.
New HIV Vaccine Target Discovered
NIH-Led team have discovered a new vaccine target site on HIV.
Mimicking Evolution to Create Novel Proteins
A study by researchers in the Kuhlman lab offers a new route to design the 'cellular machines' needed to understand and battle diseases.
Antibody Therapy Opens Door to Potential New Treatment for HIV
Researchers at Rockefeller University show how a broadly neutralizing antibody could be used to help fight HIV.
Investigational Malaria Vaccine Protects Healthy U.S. Adults
Researchers at NIH have found that the malaria vaccine protected a small number of healthy, malaria-naïve adults in the U.S. from infection for more than one year after immunization.
SELECTBIO

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,100+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!