deletion of the rnaseiii enzyme dicer in thyroid follicular cells causes hypothyroidism with signs of neoplastic alterations删除rnaseiii酶的帽子在甲状腺滤泡细胞导致甲状腺功能减退与肿瘤改变的迹象.pdfVIP

Deletion of the RNaseIII Enzyme Dicer in Thyroid Follicular Cells Causes Hypothyroidism with Signs of Neoplastic Alterations 1 1 ´ 1 2 2 Wendy Rodriguez , Ling Jin , Veronique Janssens , Christophe Pierreux , Anne-Christine Hick , Eneko 1 1 Urizar , Sabine Costagliola * ´ ´ ´ ´ 1 Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire (I.R.I.B.H.M.), Faculte de Medecine, Universite Libre de Bruxelles (ULB), Brussels, Belgium, 2 Christian de Duve Institute (UCL), Brussels, Belgium Abstract 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 mutan