A mouse model for hereditary thyroid dysgenesis and cleft palate
A mouse model for hereditary thyroid dysgenesis and cleft palate
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DOI：
10.1038/1289
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发表时间：
1998-08-01
期刊：
影响因子：
30.8
通讯作者：
Di Lauro, R
中科院分区：
文献类型：
--
作者：
De Felice, M;Ovitt, C;Di Lauro, R
甲状腺形态发生改变(甲状腺发育不良)是一种常见的人类畸形。在每三千到四千名新生儿中就有一人被检测到先天性甲状腺功能减退，其中80%要么有异位、小和舌下甲状腺，要么没有甲状腺组织(1)。这些病例大多数是零星出现的，尽管有少数复发的家族性甲状腺发育不全的病例已被描述(2)。缺乏遗传性甲状腺发育不良的证据可能与甲状腺功能减退的严重程度有关。新生儿筛查和早期甲状腺激素治疗已经消除了甲状腺功能减退的大部分临床后果，因此这种疾病的遗传性可能在不久的将来变得明显。我们最近克隆了编码含有叉头区的转录因子TTF-2的基因，并将该基因的位置命名为TITF2，定位于小鼠的4号染色体(参考文献4)。3)。TITF2表达于发育中的甲状腺、大部分前肠内胚层和颅咽外胚层，包括Rathke囊(3)。Tif2在甲状腺前体细胞中的表达随着其停止迁移而下调，提示该因子参与了甲状腺的形态发生过程。在这里，我们显示了TITF2缺失的突变小鼠表现出腭裂和舌下甲状腺或完全缺失的甲状腺。因此，TITF2(-/-)突变会导致新生儿甲状腺功能减退，这与人类的甲状腺发育不全相似。
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(1). Most of these cases appear sporadically, although a few cases of recurring familial thyroid dysgenesis have been described(2). 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(3). 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.