Zinkevich Natalya S, Bosenko Dmitry V, Link Brian A, Semina Elena V
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
BMC Dev Biol. 2006 Mar 7;6:13. doi: 10.1186/1471-213X-6-13.
Laminins represent major components of basement membranes and play various roles in embryonic and adult tissues. The functional laminin molecule consists of three chains, alpha, beta and gamma, encoded by separate genes. There are twelve different laminin genes identified in mammals to date that are highly homologous in their sequence but different in their tissue distribution. The laminin alpha -1 gene was shown to have the most restricted expression pattern with strong expression in ocular structures, particularly in the developing and mature lens.
We identified the zebrafish lama1 gene encoding a 3075-amino acid protein (lama1) that possesses strong identity with the human LAMA1. Zebrafish lama1 transcripts were detected at all stages of embryo development with the highest levels of expression in the developing lens, somites, nervous and urogenital systems. Translation of the lama1 gene was inhibited using two non-overlapping morpholino oligomers that were complementary to sequences surrounding translation initiation. Morphant embryos exhibited an arrest in lens development and abnormalities in the body axis length and curvature.
These results underline the importance of the laminin alpha 1 for normal ocular development and provide a basis for further analysis of its developmental roles.
层粘连蛋白是基底膜的主要成分，在胚胎和成年组织中发挥多种作用。功能性层粘连蛋白分子由α、β和γ三条链组成，由不同基因编码。迄今为止，在哺乳动物中已鉴定出12种不同的层粘连蛋白基因，它们在序列上高度同源，但在组织分布上有所不同。层粘连蛋白α-1基因显示出最受限的表达模式，在眼部结构中表达强烈，特别是在发育中的和成熟的晶状体中。
我们鉴定出斑马鱼lama1基因，其编码一种3075个氨基酸的蛋白质（lama1），与人LAMA1具有高度同源性。在胚胎发育的所有阶段都检测到斑马鱼lama1转录本，在发育中的晶状体、体节、神经和泌尿生殖系统中表达水平最高。使用两种与翻译起始周围序列互补的非重叠吗啉代寡聚物抑制lama1基因的翻译。突变胚胎表现出晶状体发育停滞以及体轴长度和曲率异常。
这些结果强调了层粘连蛋白α1对正常眼部发育的重要性，并为进一步分析其发育作用提供了基础。
