Yamada G, Mansouri A, Torres M, Stuart E T, Blum M, Schultz M, De Robertis E M, Gruss P
Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Development. 1995 Sep;121(9):2917-22. doi: 10.1242/dev.121.9.2917.
The goosecoid gene encodes a homeodomain-containing protein that has been identified in a number of species and has been implicated in a variety of key developmental processes. Initially suggested to be involved in organizing the embryo during early development, goosecoid has since been demonstrated to be expressed during organogenesis-most notably in the head, the limbs and the ventrolateral body wall. To investigate the role of goosecoid in embryonic development, we have inactivated the gene by gene targeting to generate mice mutant for the goosecoid gene. Mice that are homozygous for the goosecoid mutation do not display a gastrulation phenotype and are born; however, they do not survive more than 24 hours. Analysis of the homozygotes revealed numerous developmental defects affecting those structures in which goosecoid is expressed during its second (late) phase of embryonic expression. Predominantly, these defects involve the lower mandible and its associated musculature including the tongue, the nasal cavity and the nasal pits, as well as the components of the inner ear (malleus, tympanic ring) and the external auditory meatus. Although the observed phenotype is in accordance with the late expression domains of goosecoid in wild-type embryos, we suggest that the lack of an earlier phenotype is the result of functional compensation by other genes.
鹅膏蕈氨酸基因编码一种含同源结构域的蛋白质，该蛋白质已在多个物种中被鉴定出来，并与多种关键的发育过程有关。最初有人认为它在早期发育过程中参与胚胎的组织构建，此后已证明它在器官发生过程中表达——最显著的是在头部、四肢和腹侧体壁。为了研究鹅膏蕈氨酸在胚胎发育中的作用，我们通过基因打靶使该基因失活，以产生鹅膏蕈氨酸基因突变的小鼠。鹅膏蕈氨酸突变纯合子小鼠没有表现出原肠胚形成表型并出生；然而，它们存活时间不超过24小时。对纯合子的分析揭示了许多发育缺陷，这些缺陷影响了鹅膏蕈氨酸在胚胎表达的第二（晚期）阶段所表达的那些结构。主要地，这些缺陷涉及下颌骨及其相关肌肉组织，包括舌头、鼻腔和鼻凹，以及内耳（锤骨、鼓膜环）和外耳道的组成部分。尽管观察到的表型与野生型胚胎中鹅膏蕈氨酸的晚期表达区域一致，但我们认为早期表型的缺失是其他基因功能补偿的结果。
