Bush Jeffrey O, Lan Yu, Maltby Kathleen M, Jiang Rulang
Department of Biology, University of Rochester, Rochester, New York 14642, USA.
Dev Dyn. 2002 Nov;225(3):322-6. doi: 10.1002/dvdy.10154.
Mutations in the TBX22 gene have been identified recently in patients with the X-linked cleft palate and ankyloglossia syndrome, suggesting that the TBX22 transcription factor plays an important role in palate development. However, because ankyloglossia has been reported in the majority of patients with TBX22 mutations, it has been speculated that the cleft palate phenotype is secondary to defective fetal tongue movement. To understand the role of TBX22 in disease pathogenesis and in normal development, it is necessary to carry out a detailed temporal and spatial gene expression analysis. We report here the isolation and developmental expression analysis of the mouse homolog Tbx22. The mouse Tbx22 gene encodes a putative protein of 517 amino acid residues, which shares 72% overall amino acid sequence identity with the human TBX22 protein. By using interspecific backcross analysis, we have localized the Tbx22 gene to mouse chromosome X, in a region syntenic to human chromosome Xq21, where the TBX22 gene resides, indicating that Tbx22 is the ortholog of human TBX22. Our in situ hybridization analysis shows that Tbx22 is expressed in a temporally and spatially highly restricted pattern during mouse palate and tongue development. Together with the mutant phenotypes in human patients, our data indicate a primary role for Tbx22 in both palate and tongue development.
最近在患有X连锁腭裂和舌系带过短综合征的患者中发现了TBX22基因突变，这表明TBX22转录因子在腭部发育中起重要作用。然而，由于在大多数TBX22基因突变患者中都报告有舌系带过短，因此有人推测腭裂表型是胎儿舌运动缺陷的继发结果。为了了解TBX22在疾病发病机制和正常发育中的作用，有必要进行详细的时空基因表达分析。我们在此报告小鼠同源基因Tbx22的分离及发育表达分析。小鼠Tbx22基因编码一个由517个氨基酸残基组成的推定蛋白，该蛋白与人类TBX22蛋白的整体氨基酸序列同一性为72%。通过种间回交分析，我们已将Tbx22基因定位到小鼠X染色体上，该区域与人类TBX22基因所在的Xq21染色体区域同线，这表明Tbx22是人类TBX22的直系同源基因。我们的原位杂交分析表明，Tbx22在小鼠腭部和舌部发育过程中以时空高度受限的模式表达。结合人类患者的突变表型，我们的数据表明Tbx22在腭部和舌部发育中均起主要作用。
