Marotta, Pina (2010) Role of Pax8 transcriptional factor in the differentiated thyroid. [Tesi di dottorato] (Inedito)

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Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: Role of Pax8 transcriptional factor in the differentiated thyroid
Autori:
AutoreEmail
Marotta, Pinamarotta@biogem.it
Data: 30 Novembre 2010
Numero di pagine: 76
Istituzione: Università degli Studi di Napoli Federico II
Dipartimento: Biologia e patologia cellullare e molecolare "L. Califano"
Scuola di dottorato: Medicina molecolare
Dottorato: Oncologia ed endocrinologia molecolare
Ciclo di dottorato: 22
Coordinatore del Corso di dottorato:
nomeemail
Santoro, Massimo[non definito]
Tutor:
nomeemail
De Felice, Mario[non definito]
Data: 30 Novembre 2010
Numero di pagine: 76
Parole chiave: Pax8; thyroid; thyroid differentiation
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare
Area 06 - Scienze mediche > MED/13 - Endocrinologia
Area 05 - Scienze biologiche > BIO/18 - Genetica
Depositato il: 13 Dic 2010 15:08
Ultima modifica: 30 Apr 2014 19:45
URI: http://www.fedoa.unina.it/id/eprint/8201
DOI: 10.6092/UNINA/FEDOA/8201

Abstract

In Pax8-/- mice the thyroid anlage disappears around E11.5. At birth the gland appears as a rudimentary structure composed only of C cells while thyroid follicular cells are undetectable. Thus, this model does not allow the study of Pax8 function in the postnatal thyroid. To address the role of Pax8 in the differentiated thyroid, I established novel strains amenable to thyroid follicular cell-specific conditional knockout of Pax8 gene using the Cre/lox system. A genetically modified mouse strain (Pax8fl/fl) harbouring a floxed allele of Pax8 was generated. These mice were crossed with two different Cre mice, a Pax8Cre/+ strain expressing constitutively Cre recombinase by embryonic day 8.5 and a Tg-CreER strain in which Cre is active in thyroid follicular cells following tamoxifen injection. Pax8Cre/fl mice do not display an overt phenotype during embryonic life. However, 3-week old Pax8Cre/fl pups show a hypothyroid phenotype characterized by both an increased serum TSH value and a significant reduction in body weight when compared with their wild type littermates. In Pax8Cre/fl animals the thyroid gland is hypoplastic and shows the absence of the follicular structure; moreover, the expression of many thyroid specific genes, required for both hormone production and regulative functions, is completely abolished. In addition, survival of follicular cells is impaired. The disruption of Pax8 in adult life (Pax8ko/fl;Tg-CreER strain) seems to be not efficient and thyroid structure appears comparable to that of wild type. However, the absence of a clear phenotype in the Pax8ko/fl;TgCreER thyroid could be due to the compensatory proliferation of cells in which Pax8 has not been inactivated. In conclusion, in my thesis work I demonstrated in vivo that Pax8 plays a key role in controlling both the expression of many thyroid specific genes and the survival of thyroid follicular cells.

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