Identification of potential molecular mechanism related to craniofacial dysmorphism caused by FOXI3 deficiency
Identification of potential molecular mechanism related to craniofacial dysmorphism caused by FOXI3 deficiency
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DOI：
10.1002/mgg3.2411
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发表时间：
2024-03-01
影响因子：
2
通讯作者：
Huang，Xueshuang
中科院分区：
文献类型：
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作者：
Xing，Xiao-Liang;Zeng，Ziqiang;Huang，Xueshuang
半面巨大儿（Hemifacial macrosomia，HFM，OMIM 164210）是一种复杂的高度异质性疾病，FOXI 3是HFM的易感基因，FOXI 3功能缺失的小鼠表现出类似颅面畸形的表型。然而，FOXI 3缺陷导致HFM的具体发病机制至今仍不清楚。（Foxi 3 −/−）小鼠模型验证Foxi 3 −/−小鼠的颅面表型，然后利用RNAseq数据进行基因差异表达分析筛选候选致病基因，并利用定量真实的时间PCR进行基因表达验证分析。我们发现存在颅面畸形。综合生物信息学分析结果提示，Foxi 3缺陷导致的颅面畸形可能与PI 3 K-Akt信号通路有关。真实的实时定量PCR结果显示，Foxi 3-/-小鼠脑组织中PI 3 K-Akt信号通路相关基因Akt 2的表达明显增加。结论Foxi 3缺乏导致的颅面畸形可能与Akt 2和PI 3 K-Akt信号通路的表达有关。本研究为进一步了解FOXI 3的功能以及FOXI 3功能障碍导致的相关颅面畸形的发病机制和治疗奠定了基础。
BackgroundHemifacial macrosomia (HFM, OMIM 164210) is a complex and highly heterogeneous disease.FORKHEAD BOX I3(FOXI3) is a susceptibility gene for HFM, and mice with loss of function ofFoxi3did exhibit a phenotype similar to craniofacial dysmorphism. However, the specific pathogenesis of HFM caused byFOXI3deficiency remains unclear till now.MethodIn this study, we first constructed aFoxi3deficiency (Foxi3−/−) mouse model to verify the craniofacial phenotype ofFoxi3−/−mice, and then used RNAseq data for gene differential expression analysis to screen candidate pathogenic genes, and conducted gene expression verification analysis using quantitative real‐time PCR.ResultsBy observing the phenotype ofFoxi3−/−mice, we found that craniofacial dysmorphism was present. The results of comprehensive bioinformatics analysis suggested that the craniofacial dysmorphism caused byFoxi3deficiency may be involved in the PI3K‐Akt signaling pathway. Quantitative real‐time PCR results showed that the expression of PI3K‐Akt signaling pathway‐related geneAkt2was significantly increased inFoxi3−/−mice.ConclusionThe craniofacial dysmorphism caused by the deficiency ofFoxi3may be related to the expression ofAkt2and PI3K‐Akt signaling pathway. This study laid a foundation for understanding the function ofFOXI3and the pathogenesis and treatment of related craniofacial dysmorphism caused byFOXI3dysfunction.