title: NF-κB Essential Modulator (NEMO) Is Critical for Thyroid Function.
abstract: The I-κB kinase (IKK) subunit NEMO/IKKγ (NEMO) is an adapter molecule that is critical for canonical activation of NF-κB, a pleiotropic transcription factor controlling immunity, differentiation, cell growth, tumorigenesis, and apoptosis. To explore the functional role of canonical NF-κB signaling in thyroid gland differentiation and function, we have generated a murine strain bearing a genetic deletion of the NEMO locus in thyroid. Here we show that thyrocyte-specific NEMO knock-out mice gradually develop hypothyroidism after birth, which leads to reduced body weight and shortened life span. Histological and molecular analysis indicate that absence of NEMO in thyrocytes results in a dramatic loss of the thyroid gland cellularity, associated with down-regulation of thyroid differentiation markers and ongoing apoptosis. Thus, NEMO-dependent signaling is essential for normal thyroid physiology.
authors.affiliation: From the Biogem Consortium, Via Camporeale, 83031 Ariano Irpino, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Reale
authors.affiliation: From the Biogem Consortium, Via Camporeale, 83031 Ariano Irpino, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Iervolino
authors.affiliation: From the Biogem Consortium, Via Camporeale, 83031 Ariano Irpino, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Scudiero
authors.affiliation: From the Biogem Consortium, Via Camporeale, 83031 Ariano Irpino, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Ferravante
authors.affiliation: From the Biogem Consortium, Via Camporeale, 83031 Ariano Irpino, Italy.
authors.forename: Luca Egildo
authors.initials: LE
authors.lastname: D'Andrea
authors.affiliation: From the Biogem Consortium, Via Camporeale, 83031 Ariano Irpino, Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Mazzone
authors.affiliation: the Dipartimento di Scienze e Tecnologie, Università del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Zotti
authors.affiliation: the Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli, 80131 Napoli, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Leonardi
authors.affiliation: From the Biogem Consortium, Via Camporeale, 83031 Ariano Irpino, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Roberto
authors.affiliation: the Istituto di Endocrinologia e Oncologia Sperimentale, CNR, Napoli, Italy.
authors.forename: Mariastella
authors.initials: M
authors.lastname: Zannini
authors.affiliation: the Istituto di Endocrinologia e Oncologia Sperimentale, CNR, Napoli, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: de Cristofaro
authors.affiliation: the Laboratory Animal Research Centre, Qatar University, PO Box 2713, Doha, Qatar.
authors.forename: Muralitharan
authors.initials: M
authors.lastname: Shanmugakonar
authors.affiliation: From the Biogem Consortium, Via Camporeale, 83031 Ariano Irpino, Italy,; the Dipartimento di Scienze Cardio-toraciche e Respiratorie, Seconda Università di Napoli, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Capasso
authors.affiliation: the Institute for Genetics, University of Cologne, 50923 Cologne, Germany, and.
authors.forename: Manolis
authors.initials: M
authors.lastname: Pasparakis
authors.affiliation: From the Biogem Consortium, Via Camporeale, 83031 Ariano Irpino, Italy,; the Dipartimento di Scienze e Tecnologie, Università del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy,. Electronic address: vito@unisannio.it.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Vito
authors.affiliation: the Dipartimento di Scienze e Tecnologie, Università del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy,; the Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli, 80131 Napoli, Italy.
authors.forename: Romania
authors.initials: R
authors.lastname: Stilo
mesh_terms: D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D005260:Female; D017353:Gene Deletion; D007037:Hypothyroidism / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism* / Q000473:pathology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C514981:NEMO protein, mouse; D016328:NF-kappa B
keywords: NF-kappaB; NF-kappaB transcription factor; apoptosis; signal transduction; thyroid; thyroid hormone