A mouse model demonstrates a multigenic origin of congenital hypothyroidism.

Abstract:

: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 TSH receptor 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 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 TD can be of multigenic origin in mice and strongly suggest that a similar pathogenic mechanism may be observed in humans.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Amendola E,De Luca P,Macchia PE,Terracciano D,Rosica A,Chiappetta G,Kimura S,Mansouri A,Affuso A,Arra C,Macchia V,Di Lauro R,De Felice M

doi

10.1210/en.2005-0882

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

5038-47

issue

12

eissn

0013-7227

issn

1945-7170

pii

en.2005-0882

journal_volume

146

pub_type

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