Navigation Links
New chimeric mouse model for human liver diseases, drug testing
Date:12/4/2007

La Jolla, CA Cells cultured in the lab are like a fish out of water. Often, their behavior does not reflect their biological function within an entire organ or organism, which, for example, turns studying human liver cells into a big challenge.

One way to get around the altered properties of the stranded cells is to populate mouse livers with human hepatocytes in the hope of creating a natural environment, which is exactly what researchers at the Salk Institute for Biological Studies did. They developed a simple system that allows them to transplant human hepatocytes into immunodeficient mice, which can now be used to test how drugs affect the liver.

Rodents are often used as model organisms to study the efficacy and toxicity of drugs, says lead author Karl-Dimiter Bissig, M.D. Ph.D., a postdoctoral researcher in the Laboratory of Genetics, but mouse and rat hepatocytes may function in very different ways when it comes to metabolism of drugs.

In the past, this has led to unexpected toxicity problems, when drugs moved into clinical trials after toxicity tests in rats failed to reveal adverse effects (e.g. Troglitazone). But it also worked the other way around. The clinical introduction of furosamide, a powerful but perfectly safe diuretic, has been slowed down because of its hepatotoxicity in rats, says Bissig.

The work, which will be published in this weeks online edition of the Proceedings of the National Academy of Sciences also holds promise for a better understanding of infectious diseases that affect the liver. It is basically impossible to grow human hepatocytes in the lab, which was a big hurdle for the study of viruses such as hepatitis A and hepatitis B, says senior author Inder Verma, Ph.D., a professor in the Laboratory of Genetics.

But most importantly, Bissig says, the mice will be an invaluable tool to advance regenerative medicine. Many inherited disorders affecting liver metabolism could be cured if only five percent of all hepatocytes would express the missing enzyme, he says.

In fact, thats the underlying principle of the Salk researchers new chimeric mouse. It is based on a murine model for hereditary tyrosinaemia type I, developed by researchers at Oregon Healthy & Science University. An enzymatic defect in the tyrosine catabolism results in a toxic accumulation of byproducts within hepatocytes unless the mice are treated with a drug called NBTC.

Withdrawing the drug allows to selectively expand hepatocytes that do not have this defect, such as transplanted human hepatocytes. Within three months of transplantation, up to 20 percent of the mouse liver is repopulated by human hepatocytes. But whats more, the transplanted cells keep producing a foreign protein slipped inside with the help of a lentiviral vector, the kind usually used for gene therapy. We are very excited about that aspect since very often cells shut off the production of proteins introduced as part of gene therapy, says Verma.


'/>"/>

Contact: Gina Kirchweger
kirchweger@salk.edu
858-453-4100 x1340
Salk Institute  
Source:Eurekalert

Related biology news :

1. A computer for your mouse!
2. Immune cells promote blood vessel formation in mouse endometriosis
3. Cancer-resistant mouse discovered
4. Looking through the eyes of a mouse, scientists monitor circulating cells in its bloodstream
5. Novel 3-D cell culture model shows selective tumor uptake of nanoparticles
6. A new kind of rat model
7. JILA finds flaw in model describing DNA elasticity
8. Smithsonian researchers develop models to assess wetland health
9. Prediction of RNA pseudoknots using heuristic modeling with mapping and sequential folding
10. Simulating kernel production influences maize model accuracy
11. MIT model could improve some drugs effectiveness
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
New chimeric mouse model for human liver diseases, drug testing
(Date:4/15/2016)... 2016 Research and Markets has ... Market 2016-2020,"  report to their offering.  , ... ,The global gait biometrics market is expected to ... period 2016-2020. Gait analysis generates multiple ... used to compute factors that are not or ...
(Date:3/31/2016)... March 31, 2016   ... or the "Company") LegacyXChange is excited to ... its soon to be launched online site for trading ... ) will also provide potential shareholders a sense ... technology to an industry that is notorious for fraud. ...
(Date:3/23/2016)... 2016 Einzigartige ... und Stimmerkennung mit Passwörtern     ... MESG ), ein führender Anbieter digitaler Kommunikationsdienste, ... SpeechPro zusammenarbeitet, um erstmals dessen Biometrietechnologie einzusetzen. ... Möglichkeit angeboten, im Rahmen mobiler Apps neben ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... , ... Supplyframe, the Industry Network for electronics hardware design ... Located in Pasadena, Calif., the Design Lab’s mission is to bring together inventors ... and brought to market. , The Design Lab is Supplyframe’s physical representation of ...
(Date:6/23/2016)... Calif. , June 23, 2016  Blueprint Bio, ... biological discoveries to the medical community, has closed its ... Matthew Nunez . "We have received ... with the capital we need to meet our current ... essentially provide us the runway to complete validation on ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... regulatory and technical consulting, provides a free webinar on Performing Quality ... 13, 2016 at 12pm CT at no charge. , Incomplete investigations are still ...
(Date:6/22/2016)... DIEGO , June 22, 2016 ... that will allow them to produce up to ... from one lot within one week. These high-quality, ... time laboriously preparing cells and spend more time ... possible through a proprietary, high-volume manufacturing process that ...
Breaking Biology Technology: