Genetic deletion of the EGFR ligand epigen does not affect mouse embryonic development and tissue homeostasis
Genetic deletion of the EGFR ligand epigen does not affect mouse embryonic development and tissue homeostasis
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DOI：
10.1016/j.yexcr.2012.11.001
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发表时间：
2013-02-15
影响因子：
3.7
通讯作者：
Schneider, Marlon R.
中科院分区：
文献类型：
--
作者：
Dahlhoff, Maik;Schaefer, Matthias;Schneider, Marlon R.
表皮生长因子受体（EGFR）是一种酪氨酸激酶受体，在发育、组织稳态和疾病过程中具有多种功能。EGFR活化、同源二聚体或异源二聚体（与相关ERBB 2 -4受体）的形成和下游信号传导由结构相关生长因子家族（EGFR配体）的结合引发。基因缺失实验阐明了所有家庭成员的生物学功能，除了最后的特征配体，epigen。我们在小鼠胚胎干细胞中采用基因靶向来产生缺乏epigen表达的小鼠。epigen的丧失不影响小鼠的发育、生育能力或器官生理学。定量RT-PCR分析显示，表观基因缺陷小鼠的一些器官中β细胞素和EGF的表达增加，表明这些配体具有功能性补偿作用。总之，我们完成了EGFR配体的遗传分析，并表明epigen具有非必需的功能或在生长和组织稳态过程中可以由其他EGFR配体补偿的功能。(C)2012 Elsevier Inc. All rights reserved.
The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor with manifold functions during development, tissue homeostasis and disease. EGFR activation, the formation of homodimers or heterodimers (with the related ERBB2-4 receptors) and downstream signaling is initiated by the binding of a family of structurally related growth factors, the EGFR ligands. Genetic deletion experiments clarified the biological function of all family members except for the last characterized ligand, epigen. We employed gene targeting in mouse embryonic stem cells to generate mice lacking epigen expression. Loss of epigen did not affect mouse development, fertility, or organ physiology. Quantitative RT-PCR analysis revealed increased expression of betacellulin and EGF in a few organs of epigen-deficient mice, suggesting a functional compensation by these ligands. In conclusion, we completed the genetic analysis of EGFR ligands and show that epigen has non-essential functions or functions that can be compensated by other EGFR ligands during growth and tissue homeostasis. (C) 2012 Elsevier Inc. All rights reserved.