A mouse model for hereditary thyroid dysgenesis and cleft palate

Mario De Felice, Catherine Ovitt, Elio Biffali, Alina Rodriguez-Mallon, Claudio Arra, Konstantinos Anastassiadis, Paolo Emidio Macchia, Marie Genevieve Mattei, Angela Mariano, Hans Schöler, Vincenzo Macchia, Roberto Di Lauro

Research output: Contribution to journalArticlepeer-review


Alteration of thyroid gland morphogenesis (thyroid dysgenesis) is a frequent human malformation. Among the one in three to four thousand newborns in which congenital hypothyroidism is detected, 80% have either an ectopic, small and sublingual thyroid, or have no thyroid tissue. Most of these cases appear sporadically, although a few cases of recurring familial thyroid dysgenesis have been described. The lack of evidence for hereditary thyroid dysgenesis may be due to the severity of the hypothyroid phenotype. Neonatal screening and early thyroid hormone therapy have eliminated most of the clinical consequences of hypothyroidism such that the heritability of this condition may become apparent in the near future. We have recently cloned cDNA encoding a forkhead domain-containing transcription factor, TTF-2, and have located the position of the gene, designated Titf2, to mouse chromosome 4 (ref. 3). Titf2 is expressed in the developing thyroid, in most of the foregut endoderm and in craniopharyngeal ectoderm, including Rathke's pouch. Expression of Titf2 in thyroid cell precursors is down-regulated as they cease migration, suggesting that this factor is involved in the process of thyroid gland morphogenesis. Here we show that Titf2-null mutant mice exhibit cleft palate and either a sublingual or completely absent thyroid gland. Thus, mutation of Titf2(-/-) results in neonatal hypothyroidism that shows similarity to thyroid dysgenesis in humans.

Original languageEnglish
Pages (from-to)395-398
Number of pages4
JournalNature Genetics
Issue number4
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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