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Projects / Programmes source: ARIS

Development of transgenic mouse models to study the function of Cyp51 and Raidd genes

Research activity

Code Science Field Subfield
4.06.00  Biotechnical sciences  Biotechnology   

Code Science Field
T490  Technological sciences  Biotechnology 
B220  Biomedical sciences  Genetics, cytogenetics 
Keywords
transgenic model, conditional knockout, Cyp51, spermatogenesis, Raidd, TNF-alpha
Evaluation (rules)
source: COBISS
Researchers (2)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  10412  PhD Simon Horvat  Biotechnical sciences  Head  2005 - 2007  561 
2.  21397  PhD Helena Motaln  Biochemistry and molecular biology  Researcher  2005 - 2007  207 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0481  University of Ljubljana, Biotechnical Faculty  Ljubljana  1626914  66,215 
Abstract
Lanosterol 14-demethylase encoded by the Cyp51 gene has an important housekeeping role (e.g., cholesterol biosynthesis) and in producing meiosis-activating sterols (MAS) in germ cells. The function of MAS and hence Cyp51 has been implicated in meiosis and germ cell maturation primarily by in vitro experiments. However, the in vivo role of Cyp51 and MAS in the germ cell development is unclear. In this grant application we propose to develop a transgenic mouse model that would allow us to examine in vivo role of Cyp51 (and MAS) in male germ development (and later in other tissues). As homozygous null condition for Cyp51 would most likely result in embryo lethality we will use conditional transgenic technology to produce mice that lack Cyp51 in the male germ cells only. The proposed research is clearly of a fundamental nature by its aims but should potentially lead to results of interest for the clinical field. Improved knowledge of the role of Cyp51 and MAS in regulating germinal differentiation could elucidate the causes of numerous, mostly unexplained cases of male sterility and provide novel therapeutic treatments. A second set of proposed experiments attempt to further characterize the function of the Raidd gene for which we have previously developed transgenic mouse models and ES-cell model. Proposed experiments aim to examine the effect of TNFon transgenic ES clones that lack the Raidd gene. If Raidd functions via the TNFsignalling pathway in early embryogenesis we expect to observe some sort of »resistance« of Raidd-/- ES cells to the TNF anti-differentiation effect. Results should contribute new knowledge regarding the mechanisms of Raidd's action during early mouse embryogenesis and open new avenues for applications such as improved IVF methods for culturing human embryos. While the animal transgenic technology is widely used to study gene function in developed world, it is not yet available in Slovenia. One of the non-scientific aims of this grant proposal is to help introduce this technology to Slovenia. Funding is requested for a postdoctoral scientist who has been trained abroad during graduate studies in animal transgenic technology to perform the first such experiments in Slovenia .
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