| title: | Molecular mechanisms of the gelatinous drop-like corneal dystrophy |
|---|---|
| reg no: | ETF5309 |
| project type: | Estonian Science Foundation research grant |
| subject: |
3. Medical Sciences |
| status: | completed |
| institution: | University of Tartu |
| head of project: | Pait Teesalu |
| duration: | 01.01.2002 - 31.12.2004 |
| description: | Gelatinous drop-like corneal dystrophy (GDLD) is a progressive autosomal recessive disorder, characterized by severe corneal amyloidosis leading to blindness. In 1999 the M1S1 gene was identified as the disease-causing gene of GDLD and four mutations were identified among Japanese patients. Investigating GDLD disease cases found in Estonia, we discovered a new mutation in M1S1 gene - ins520C and a single nucleotide polymorphism - 518A/C. Probably the mutation found by us and not described in oriental populations could also be found in other patients among European descendants. Although changes at DNA level responsible for GDLD have been identified, it is not known how the abnormal M1S1 product causes the disease. Continuing our GDLD studies we hope to clarify the main aspects of pathological processes leading to formation of amyloid in GDLD patients. The main aim of the study is to discover, which changes at structural and functional level are caused by the mutation and polymorphism, found by us in M1S1 gene, and how the mutation leads to formation of disease. We have hypothesed that impaired M1S1 protein has differences in cellular localization and tissue distribution as compared to the normal M1S1 gene product. We also think that the biological functions of abnormal M1S1 protein might be altered. In addition we plan to find out whether there are functional differences between allelic forms of non-mutated M1S1 protein. To achive the goals mentioned above we will clone the M1S1 gene, express the protein in E.coli strain and produce monoclonal antibodies against mutated protein as well as against allelic forms of nonmutated M1S1. Using antibodies produced, we will perform immunohistochemical studies. Besides research of biological functions of mutated and non-mutated M1S1 protein will be carried on. Investigating the local form of amyloidosis - GDLD, we plan to use it as a model to describe the general aspects of molecular mechanisms of amyloidoses. Having knowledge about GDLD we can perform genetic counselling and if needed, perform the prenatal diagnosis. The information obtained can also serve as a basis to develop therapy for helping GDLD patients. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Erkki Juronen | Inst Gen& Mol Pathol, U of Tartu | senior scientist | |
| 2. | Aavo Lang | Inst Physiol, Univ of Tartu | docent | |
| 3. | Gunnar Tasa | Dept HumBiol & Gen, U of Tartu | scientist | |
| 4. | Pait Teesalu | Eye Clinic, University of Tartu | Head of the Clinic | |