Granadino B, Gallardo M E, López-Ríos J, Sanz R, Ramos C, Ayuso C, Bovolenta P, Rodríguez de Córdoba S
Departamento de Inmunología, Centro de Investigaciones Biológicas Consejo Superior de Investigaciones Científicas, Velázquez 144, Madrid, 28006, Spain.
Genomics. 1999 Jan 1;55(1):100-5. doi: 10.1006/geno.1998.5611.
The Drosophila gene sine oculis (so) is a nuclear homeoprotein that is required for eye development. Homologous genes to so, denoted SIX genes, have been found in vertebrates. Among the SIX genes, SIX3 is considered to be the functional homologue of so. To provide insight into the potential implications of SIX3 in human ocular malformations, we have cloned and characterized the human SIX3 gene. In human eye, SIX3 produces a 3-kb transcript that codes for a 332-amino-acid polypeptide that is virtually identical to its mouse and chick homologues. Expression of SIX3 was detected in human embryos as early as 5-7 weeks of gestation and found to be maintained in the eye throughout the entire period of fetal development. At 20 weeks of gestation, expression of SIX3 in the human retina was detected in the ganglion cells and in cells of the inner nuclear layer. The human SIX3 gene spans 4.4 kb of genomic DNA and is split in two exons separated by a 1659-bp intron. SIX3 was mapped to human chromosome 2p16-p21, between the genetic markers D2S119 and D2S288. Interestingly, the map position of human SIX3 overlaps the locations of two dominant disorders with ocular phenotypes that have been assigned to this chromosomal region, holoprosencephaly type 2 and Malattia Leventinese.
果蝇的无眼基因（so）是一种核内同源结构域蛋白，是眼睛发育所必需的。在脊椎动物中发现了与so同源的基因，称为SIX基因。在SIX基因中，SIX3被认为是so的功能同源物。为了深入了解SIX3在人类眼部畸形中的潜在影响，我们克隆并鉴定了人类SIX3基因。在人眼中，SIX3产生一个3kb的转录本，编码一个332个氨基酸的多肽，该多肽与其小鼠和鸡的同源物几乎相同。早在妊娠5-7周时就在人类胚胎中检测到SIX3的表达，并且发现在胎儿发育的整个过程中在眼中持续存在。在妊娠20周时，在神经节细胞和内核层细胞中检测到人类视网膜中SIX3的表达。人类SIX3基因跨越4.4kb的基因组DNA，被一个1659bp的内含子分隔为两个外显子。SIX3被定位到人类染色体2p16-p21，位于遗传标记D2S119和D2S288之间。有趣的是，人类SIX3的图谱位置与两种具有眼部表型的显性疾病的位置重叠，这两种疾病已被定位到该染色体区域，即2型全前脑畸形和莱万廷内斯病。
