| title: | Study of kidney and inner ear deficiencies using transgenic mice |
|---|---|
| reg no: | ETF5265 |
| project type: | Estonian Science Foundation research grant |
| subject: |
1.9. Genetics, Physiology and Microbiology 1.15. Zoology 3. Medical Sciences |
| status: | completed |
| institution: | University of Tartu |
| head of project: | Illar Pata |
| duration: | 01.01.2002 - 31.12.2003 |
| description: | Transcription factors of the paired-box family (Pax factors) are essential in morphogenesis of various organ systems. Pax2 deficiency causes kidney and inner ear defects in humans and mice. Recently we have found that defects in Pax2 knockout mice resemble closely these caused by inactivation of the transcription factor GATA3 gene, but are less severe. Pax2 is coexpressed with a related gene, Pax8, in the inner ear and kidney, and since redundancy between Pax proteins is common, Pax2 and Pax8 may partially compensate for each others function. Here, we want to explore the relationship between Pax2 and Pax8 in kidney and inner ear morphogenesis by generating Pax2/Pax8 double knockout mice. We will study phenotype of embryos carrying distinct combinations of mutant alleles, focusing primarily to ear and kidney defects. We employ gene expression analysis methods (in situ hybridisation, immunolabelling and reverse transcription-PCR to microdissected tissues), and combine these with histological and cell death and proliferation analysis. Further, this model will enable us to study regulatory relationships between Pax genes and other genes that have been assigned crucial functions in kidney and/or inner ear. The latter include GATA3, Nkx5.1, Foxi1, and GDNF signalling genes. In parallel, gene expression analyses will be carried out in GATA3 knockout mice. As a result, the project will reveal Pax2 and Pax8 functions and their mutual redundancy in vivo, as well as their relationship to other essential genes in development. This will help to understand the molecular mechanisms of kidney and inner ear diseases. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Madis Jakobson | University of Tartu | PhD stud | |
| 2. | Kersti Lilleväli | University of Tartu | PhD stud | |
| 3. | Illar Pata | University of Tartu, Faculty of Biology and Geography | research scientist | |