Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Feodor-Lynen-Str. 25, 81377 Munich, Germany.
Exp Cell Res. 2013 Feb 15;319(4):529-35. doi: 10.1016/j.yexcr.2012.11.001. Epub 2012 Nov 6.
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.
表皮生长因子受体(EGFR)是一种酪氨酸激酶受体,在发育、组织稳态和疾病中具有多种功能。EGFR 的激活、同源二聚体或异源二聚体(与相关的 ERBB2-4 受体)的形成以及下游信号转导是由一系列结构相关的生长因子,即 EGFR 配体的结合所启动的。遗传缺失实验阐明了除最后一个被表征的配体 epigen 之外的所有家族成员的生物学功能。我们利用小鼠胚胎干细胞中的基因靶向技术生成了缺乏 epigen 表达的小鼠。epgen 的缺失并不影响小鼠的发育、生育能力或器官生理学。定量 RT-PCR 分析显示,epgen 缺陷小鼠的一些器官中 betacellulin 和 EGF 的表达增加,表明这些配体具有功能补偿作用。总之,我们完成了 EGFR 配体的遗传分析,并表明 epigen 在生长和组织稳态过程中具有非必需的功能或可被其他 EGFR 配体代偿的功能。