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Contenuto archiviato il 2024-06-10

Transgenic and knockout mice models of thyroid diseases.

Obiettivo



The present project proposes to combine the expertise and previous realizations of four European groups to develop animal models representative of thyroid diseases: goiter, thyroid cancer, congenital hypothyroidism.
The thyroid is considered as representative of epithelial tissues in general. Its advantages as an object of study are the well described and easy methods for its physiological investigation, the availability of highly specific promoters and the consequent possibility of targeting the expression of any desired protein exclusively into the thyroid gland. This latter feature makes the thyroid gland an excellent model for gene therapy.
Goiter is, with diabetes, the most prevalent endocrine disease. Although rarely dangerous, it is invalidating and, often requires surgery. Its impact is therefore important in terms of quality of living and social security costs.
Thyroid tumors are the most prevalent endocrine tumors. In people over 50 years old, 50% of the thyroids have nodules, 4 to 5% of which contain a cancer. One of the major problems of modern endocrinology, exemplified by thyroid and prostate neoplasms, is the absence of fully reliable diagnostic tools to distinguish benign and potentially malignant lesions among the numerous nodules that modern technology now reveals. This leads to numerous avoidable surgical interventions with personal, social and financial consequences. Patients with anaplastic carcinoma die within a year after diagnosis.
Congenital hypothyroidism is the most prevalent congenital disease. Lack of adequate correction immediately after birth, or even before birth, causes mental impairment. Its diagnosis after or even before birth is therefore of considerable importance.
Because of the polygenic character of the diseases studied, realistic models of these diseases will probably be animals with multiple genetic defects i.e. crosses between existing and newly developed unigenic models. It is proposed to develop several gene knock-out and knock-in specifically expressed in the thyroid and crosses between these strains. The models generated will be characterized and their phenotype compared to the human diseases investigated.
The groups involved have an established reputation in the field and have already generated and will generate unigenic models involving a representative set of signal transduction proteins and specific and general transcription factors. The generation of these unigenic models and their crosses requires a joint project. The methodologies to generate and analyse the phenotype of the new models requires the competence of the four groups.
Models of these diseases will later be used to develop diagnostic tools and therapies, including gene therapy, and to study the effect of environmental factors on the pathogenesis, thus fulfilling the objectives of the work programme.

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CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: Il Vocabolario Scientifico Europeo.

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Coordinatore

UNIVERSITE LIBRE DE BRUXELLES
Contributo UE
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Indirizzo
808,Route de Lennik 808 Campus Erasme - Building C
1070 BRUXELLES
Belgio

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