TY - JOUR
T1 - A mouse model for hereditary thyroid dysgenesis and cleft palate
AU - De Felice, Mario
AU - Ovitt, Catherine
AU - Biffali, Elio
AU - Rodriguez-Mallon, Alina
AU - Arra, Claudio
AU - Anastassiadis, Konstantinos
AU - Macchia, Paolo Emidio
AU - Mattei, Marie Genevieve
AU - Mariano, Angela
AU - Schöler, Hans
AU - Macchia, Vincenzo
AU - Di Lauro, Roberto
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
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U2 - 10.1038/1289
DO - 10.1038/1289
M3 - Article
C2 - 9697704
AN - SCOPUS:17344366813
VL - 19
SP - 395
EP - 398
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 4
ER -