Rubock M J, Larin Z, Cook M, Papalopulu N, Krumlauf R, Lehrach H
Laboratory of Genome Analysis, Imperial Cancer Research Fund, London, United Kingdom.
Proc Natl Acad Sci U S A. 1990 Jun;87(12):4751-5. doi: 10.1073/pnas.87.12.4751.
We have isolated two genes, Hox-2.8 and Hox-2.9, from the mouse homeobox cluster Hox-2, located on chromosome 11. A 120-kilobase yeast artificial chromosome (YAC) containing a large region of the murine Hox-2 cluster, including 45 kilobases of sequence upstream of the most 5' gene, was cloned. The DNA sequence of the YAC is unrearranged relative to the genomic map. We have subcloned from the YAC insert a homeobox gene, Hox-2.8, whose homeodolmain is highly related to that of the Drosophila homeotic gene proboscopedia (pb). The expression pattern of Hox-2.8 during embryogenesis extends the trend established by genes from Hox-2.5 to -2.7 of successively anterior domains of expression in the neural tube. We have also subcloned and sequenced from a cosmid the labial (lab)-related Hox-2.9, the most 3' member of the cluster to date. These data lend further support to the idea of a common evolutionary origin of the mouse Hox and Drosophila HOM clusters. The YAC will enable us to construct modified forms of the Hox-2 cluster in yeast and to identify their effect on the phenotype of the animal in transgenic mouse strains.
我们从位于11号染色体上的小鼠同源异型框基因簇Hox - 2中分离出了两个基因,即Hox - 2.8和Hox - 2.9。克隆了一个120千碱基对的酵母人工染色体(YAC),它包含小鼠Hox - 2基因簇的一个大片段,包括最5'端基因上游45千碱基对的序列。该YAC的DNA序列相对于基因组图谱未发生重排。我们从YAC插入片段中进行亚克隆,得到了一个同源异型框基因Hox - 2.8,其同源结构域与果蝇同源异型基因触须足(pb)的同源结构域高度相关。Hox - 2.8在胚胎发育过程中的表达模式延续了由Hox - 2.5至 - 2.7基因所确立的趋势,即在神经管中表达的区域依次靠前。我们还从一个黏粒中进行亚克隆并测序,得到了与唇(lab)相关的Hox - 2.9,它是该基因簇迄今为止最3'端的成员。这些数据进一步支持了小鼠Hox基因簇和果蝇HOM基因簇具有共同进化起源的观点。该YAC将使我们能够在酵母中构建Hox - 2基因簇的修饰形式,并在转基因小鼠品系中鉴定它们对动物表型的影响。