The first Hungarian clone mouse is born.

 Micromanipulation and genetic reprograming group

  Complex modeling systems are essential to facilitate the post-genomic medical research by revealing functional genomic meaning of the genetic code. Transgenic, especially genetic knock-out mice catalyzed the progress, but mouse anatomy and physiology is not fully adequate to study numerous human diseases.

To bridge the gap between mouse models and treatment of human diseases, generation of transgenic laboratory animal models in rabbit and rat is needed. The lack of stable stem cell lines in most species prevented targeted genetic modifications, new tools such as nuclear replacement and gene targeting in somatic cells as a technological platform offer an opportunity for progressive disease research and pharmaceutical testing systems. The overall goal of the new team established in 2003 is to provide a new technology to produce better animal models for human medical research.

Nuclear replacement (“cloning”) methods in mouse: test of safety & reliability for generation of transgenic models

 Mouse is still the most important model species, due to the amount of knowledge generated about its genome, gene functions, and proteomics. Targeted transgenesis in the mouse species has become a versatile tool for the production of experimental models of human diseases. The availability of embryonic stem (ES) cell technology for genetic engineering provides the only direct comparison with ES or somatic cell and nuclear replacement derived individuals, carrying the same genetic modifications.

The team is working on the generation of nuclear transfer mice with genetic modifications from somatic and ES cells. Production of viable and fertile mice have been reported by nuclear replacement, however, the reasons behind the frequent deformations among foetuses and progeny are not well understood. Activation and in vitro culture methods are also important. Origin of the nuclear donor cells affects success rates, and their survival in culture varies. It has been reported that offspring of nuclear replacement parental mice were normal and fertile. All epigenetic problems in the parents seem to be erased when cell nuclei go through the germ line. If tests in the “mouse clinic” system (by collaborating partner GSF) for a wide range of parameters will demonstrate that such 2^nd and 3^rd generation cloned animals are indeed phenotypically equivalent to conventional transgenic mouse models then this would open the possibility to develop novel techniques of genetic engineering based on somatic gene targeting and nuclear replacement.  

Development of nuclear replacement in rabbit

 The rabbit offers many advantages as a non-rodent model. In collaboration with the “Mammary gland development and function” Team our goal is to develop the nuclear replacement approach and compare it with microinjection and ES cell chimera methods to create transgenic rabbits expressing human factor VIII and human alkaline phosphatase (ALP) in the milk (see details at that team).

Our team is characterising differences in the reprogramming potential of nuclei obtained from cumulus and different types of fibroblast cells, subjected to transgenic modifications (including gene targeting). In vitro development of nuclear replacement embryos is analysed, and the most promising cell lines are tested further by transfer into recipients and generation of progeny.

 Cryopreservation of cells, gametes and embryos

  In order to generate a well-standardised technological platform, banking and international distribution of the new model animals need to be developed.