Researchers' Proposals


A JAVASLAT RÖVID ÖSSZEFOGLALÁSA

Production of transgenic and knock-out mice and rats by nuclear transfer from somatic- and embryonic stem-cells for disease model and pharmaceutical testing purposes Short title: Lab animal cloning


ABSTRACT

The most recent, revolutionary development in human medicine was based on revealing the genetic background of diseases. This progress wouldn't be possible without the genetic knockout technology in mouse, which is based on the genetic manipulation of embryonic stem cell lines in this species. In other species (except to some extent humans), the lack of such cell lines limited the genetic modifications to the less refined methods, using microinjection of genes. Recent breakthrough with the somatic cell nuclear transfer technology ("cloning") opened new avenues, as the use of cell lines from somatic cells allows genetic knock-out modifications in these cells and the generation of knock-out progeny. Furthermore, mouse cloning demonstrated that this method might be more efficient than the traditional ones to generate knock-out pups.

Rat is one of the most important species for pharmacological toxicity studies. The use of genetically modified rats would allow a reduction in the number of experimental animals, while increasing the reliability of the test results. Currently no embryonic stem cell lines are available in rats to allow knock-out, however, if cloning succeed in this species, somatic cell cloning would solve this problem.

Goal of the proposal: Based on the experience of the project leader in the international field of cloning research, the consortium would allow the efficient collaboration of the project leader's team with two other leading Hungarian team in the field of transgenic animal research and embryonic stem cell technology, respectively. The overall goal is to introduce a new, human medical purpose model animal system, based on the advantages offered by the nuclear transfer technology. Two of the most important model species would be studied:

1) Generation of cloned mice from somatic- and embryonic stem cells.

2) Production of gene knock-out mice for human medical disease models, using the cloning technology, among the first in Europe.

3) Development of rat cloning technology.

The project combines research development and applied research elements, and the final results would be an internationally outstanding technological development. Furthermore, the produced transgenic mice would be used directly to promote further medical research.

The success would provide an opportunity for the Hungarian medical and pharmaceutical research to apply an important, state-of-the-art technology. In long term, the technology is expected to mature to the level, when it will become viable as a commercial service. It would provide new avenues to increase the competitiveness of Hungarian applied research in the EU and also as an international business venture. The interest expressed by British, Austrian and German teams proves that such expectations are justified, and we are planning to explore further such possibilities by applying together in the EU 6th Framework Program.


Starting date: Sept 1, 2002.


List of participants:


Co-ordinator:


Research Group on Applied Animal Genetics and Biotechnology, Hungarian Academy of Sciences and Szent Istvan University.

Project leader: András Dinnyés DVM, PhD, DSc.

Address: Páter K. u. 1, Gödöllő, 2103, Hungary

Tel.: 36-(28)- 522 000/ ext. 1642 Fax: 36-(28)-521 149

E-mail: dinnyes@yahoo.com

Role: micromanipulation, animal cloning, cell culture


Further participants:


Agricultural Biotechnology Center,

Dr. Zsuzsa Bosze, Director of Animal Biology Institute

Address; Szent-Györgyi Albert u. 4., 2100 Gödöllő, Hungary

Tel: 36-(28)-430-600

fax: 36-(28)-430-647

Role: animal facilities, micromanipulation, TG technology, ES cell technology


Research Institute of Experimental Medicine, Hungarian Academy of Sciences

Dr. Gabor Szabo

Address: Szigony u. 43., 1083 Budapest, HUNGARY

Tel: 36-1- 210-9400

fax szám: 36-1-210-9423

Role: animal facilities, micromanipulation, TG technology