| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 14, 2005
Accepted on September 1, 2005
Stazione Zoologica A. Dohrn, Laboratorio di Genetica Animale, c/o CEINGE, Naples, Italy; Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica Università Federico II, Naples, Italy; Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università Federico II, Naples, Italy; Biogem c/o CEINGE, Naples, Italy; INT Fondazione Pascale, Naples, Italy; Laboratory of Metabolism, National Cancer Institute, NHI, Bethesda, Maryland 20892, USA; MPI fur Biophysikalische Chemie, Abt. Molekulare Zellbiologie, Gottingen, Germany
* To whom correspondence should be addressed. E-mail: rdilauro{at}unina.
Congenital hypothyroidism with thyroid dysgenesis (TD) is a frequent human condition characterized by elevated levels of TSH in response to reduced thyroid hormone levels. Congenital hypothyroidism is a genetically heterogeneous disease. In the majority of cases studied no causative mutations have been identified and very often the disease does not show a Mendelian transmission. However, in approximately 5% of cases it can be a consequence of mutations in genes encoding the thyroid stimulating hormone receptor (TSHR) or the transcription factors TITF1, FOXE1 or PAX8.
We report here that in mouse models the combination of partial deficiencies in the Titf1 and Pax8 genes results in an overt TD phenotype that is absent in either of the singly deficient, heterozygous mice. The disease is characterized by a small thyroid gland, elevated levels of thyroid stimulation hormone (TSH), reduced thyroglobulin biosynthesis and high occurrence of hemiagenesis. The observed phenotype is strain specific and the pattern of transmission indicates that at least two other genes, in addition to Titf1 and Pax8, are necessary to generate the condition. These results show that in mice TD can be of multigenic origin and strongly suggest that a similar pathogenic mechanism may be observed in humans.
This article has been cited by other articles:
 |
|
 |
|
  N. Sasaki, Y. Hosoda, A. Nagata, M. Ding, J.-M. Cheng, T. Miyamoto, S. Okano, A. Asano, I. Miyoshi, and T. Agui A Mutation in Tpst2 Encoding Tyrosylprotein Sulfotransferase Causes Dwarfism Associated with Hypothyroidism Mol. Endocrinol., July 1, 2007; 21(7): 1713 - 1721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Fagman, J. Liao, J. Westerlund, L. Andersson, B.E. Morrow, and M. Nilsson The 22q11 deletion syndrome candidate gene Tbx1 determines thyroid size and positioning Hum. Mol. Genet., February 1, 2007; 16(3): 276 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Dentice, V. Cordeddu, A. Rosica, A. M. Ferrara, L. Santarpia, D. Salvatore, L. Chiovato, A. Perri, L. Moschini, C. Fazzini, et al. Missense Mutation in the Transcription Factor NKX2-5: A Novel Molecular Event in the Pathogenesis of Thyroid Dysgenesis J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1428 - 1433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Vassart and J. E. Dumont Thyroid Dysgenesis: Multigenic or Epigenetic ... or Both? Endocrinology, December 1, 2005; 146(12): 5035 - 5037. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
