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Deletion of the RNaseIII enzyme dicer in thyroid follicular cells causes hypothyroidism with signs of neoplastic alterations.

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Rodriguez, Wendy Jin, Ling Janssens, Véronique Pierreux, Christophe [UCL] Hick, Anne-Christine [UCL] Costagliola, Sabine

Micro-RNAs (miRNAs) are small non-coding RNAs that regulate gene expression, mainly at mRNA post-transcriptional level. Functional maturation of most miRNAs requires processing of the primary transcript by Dicer, an RNaseIII-type enzyme. To date, the importance of miRNA function for normal organogenesis has been demonstrated in several mouse models of tissue-specific Dicer inactivation. However, the role of miRNAs in thyroid development has not yet been addressed. For the present study, we generated mouse models in which Dicer expression has been inactivated at two different stages of thyroid development in thyroid follicular cells. Regardless of the time of Dicer invalidation, the early stages of thyroid organogenesis, preceding folliculogenesis, were unaffected by the loss of small RNAs, with a bilobate gland in place. Nevertheless, Dicer mutant mice were severely hypothyroid and died soon after weaning unless they were substituted with T4. A conspicuous follicular disorganization was observed in Dicer mutant thyroids together with a strong down regulation of Nis expression. With increasing age, the thyroid tissue showed characteristics of neoplastic alterations as suggested by a marked proliferation of follicular cells and an ongoing de-differentiation in the center of the thyroid gland, with a loss of Pax8, FoxE1, Nis and Tpo expression. Together, our data show that loss of miRNA maturation due to Dicer inactivation severely disturbs functional thyroid differentiation. This suggests that miRNAs are mandatory to fine-tune the expression of thyroid specific genes and to maintain thyroid tissue homeostasis.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2012
Language Anglais
Journal information "PLoS One" - Vol. 7, no. 1, p. e29929 (2012)
Peer reviewed yes
Publisher Public Library of Science ((United States) [S.l.])
issn 1932-6203
Publication status Publié
Affiliation UCL - SSS/DDUV - Institut de Duve
MESH Subject Animals ; Mice ; Mice, Transgenic ; Organ Specificity ; Paired Box Transcription Factors ; RNA, Messenger ; Ribonuclease III ; Thyroid Gland ; Thyroid Neoplasms ; Cell Dedifferentiation ; Cell Proliferation ; Down-Regulation ; Enzyme Activation ; Gene Deletion ; Gene Expression Regulation, Developmental ; Hypothyroidism ; Integrases
Links
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Bibliographic reference Rodriguez, Wendy ; Jin, Ling ; Janssens, Véronique ; Pierreux, Christophe ; Hick, Anne-Christine ; et. al. Deletion of the RNaseIII enzyme dicer in thyroid follicular cells causes hypothyroidism with signs of neoplastic alterations.. In: PLoS One, Vol. 7, no. 1, p. e29929 (2012)
Permanent URL http://hdl.handle.net/2078/120234