New lab mice pave way for novel studies of human infection

October 22, 2006

DALLAS - Oct. 22, 2006 - A new type of laboratory mouse developed at UT Southwestern Medical Center can fight certain infections the same way humans do, making the rodents very useful for novel studies of human-pathogen interaction and developing disease therapies.

Normal mice are not susceptible to human-specific viruses, such as Epstein Barr virus and HIV, making it hard to study and craft drugs to target the viruses. Epstein Barr is a virus that causes mononucleosis.

So UT Southwestern researchers, working with University of Minnesota collaborators, generated human-mice "chimeras" - mice implanted with human tissues and human stem cells - that developed fully functional human immune systems and infection-fighting cells, such as T cells, throughout their bodies, according to a study published online today in Nature Medicine.

The T cells in the mice even mounted a potent immune response to toxic shock syndrome and infection by Epstein Barr.

"These human-mice 'chimeras' are susceptible to a variety of human-specific viruses that couldn't be easily studied in the past, giving scientists a new way to study, develop and implement novel vaccines and therapeutics to fight human disease like cancer and AIDS," said Dr. J. Victor Garcia, professor of internal medicine at UT Southwestern and the study's senior author.

Investigators have long used mouse models to study human physiology and to test new drugs, but differences in mouse and human immune systems - and the fact that normal mice can't be infected with human-specific pathogens or produce human immune cells needed to fight them - have severely limited this line of research.

To allow these studies, researchers have developed chimeras.

In immune-deficient mice that are unable to reject human cells or tissues, researchers first implant the rodents with human tissues necessary to develop human T cells. Human blood stem cells, known as CD34+ cells, then are transplanted into the mice. CD34+ cells, which give rise to human T cells, B cells and other types of human cells that protect the body against foreign organisms and pathogens, are typically used to treat human cancer and blood and heart disorders.

In this latest study, UT Southwestern researchers and their Minnesota colleagues used this combination approach - human tissues and stem cells - to try to generate a new type of chimera that can develop T cells the same way as humans.

The resulting mice, known as Bone Marrow Liver Thymic mice (BLT mice), developed a human immune system with dramatically high human T cell and other cell counts in virtually all of their tissues, including the gut and lungs, sites of important immune response to diseases.

"The fact that virtually all human immune cells are adequately distributed in all the different mouse tissues has resulted in what is probably the most human-like immune system ever developed in mice," Dr. Garcia said.

UT Southwestern researchers tested the immune system by inducing toxic shock syndrome in the mice or infecting them with Epstein Barr virus, both deadly diseases that are known to cause a proliferation of T cells in humans. The mice produced ample human T cells to respond to each disease.

This finding highlights the potential of BLT mice to be used to study the interactions between the human immune system and viruses that target human immune cells. These viruses include HIV, dengue hemorrhagic fever and other highly pathogenic agents such as influenza, SARS, anthrax and others that are hard to study in humans. Dr. Garcia said the availability of this mouse model should pave the way for the evaluation and testing of novel drugs and approaches to treat these diseases.
Other UT Southwestern researchers involved in the study were lead author and student research assistant Michael Melkus, postdoctoral researcher Dr. Anja Wege, research associate Angela Padgett-Thomas, student research assistant Paul Denton, research assistant Florence Othieno and former instructor Joel Gatlin, currently of Arena Pharmaceuticals, Inc.

The National Institutes of Health supported the study.

About UT Southwestern Medical Center

UT Southwestern Medical Center, one of the premier medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. Its more than 1,400 full-time faculty members - including four active Nobel prize winners, more than any other medical school in the world - are responsible for groundbreaking medical advances and are committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 89,000 hospitalized patients and oversee 2.1 million outpatient visits a year.

This news release is available on our World Wide Web home page at or directly at

To automatically receive news releases from UT Southwestern via e-mail, subscribe at

Dr. J. Victor Garcia -,2356,38578,00.html

UT Southwestern Medical Center

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to