PDF(Pubmed)
Abstract：
The population sizes of different retinal cell types vary between different strains of mice, and that variation can be mapped to genomic loci in order to identify its polygenic origin. In some cases, controlling genes act independently, whereas in other instances, they exhibit epistasis. Here, we identify an epistatic interaction revealed through the mapping of quantitative trait loci from a panel of recombinant inbred strains of mice. The population of retinal horizontal cells exhibits a twofold variation in number, mapping to quantitative trait loci on chromosomes 3 and 13, where these loci are shown to interact epistatically. We identify a prospective genetic interaction underlying this, mediated by the bHLH transcription factor Neurog2, at the chromosome 3 locus, functioning to repress the LIM homeodomain transcription factor Isl1, at the chromosome 13 locus. Using single and double conditional knockout mice, we confirm the countervailing actions of each gene, and validate in vitro a crucial role for two single nucleotide polymorphisms in the 5\'UTR of Isl1, one of which yields a novel E-box, mediating the repressive action of Neurog2.
摘要：
不同视网膜细胞类型的种群大小在不同品系小鼠之间有所不同，并且该变异可以被定位到基因组基因座以识别其多基因起源。在某些情况下,控制基因独立运作，而在其他情况下，他们表现出上位性。在这里，我们确定了通过对一组重组近交系小鼠的数量性状基因座进行定位而揭示的上位相互作用。视网膜水平细胞的数量表现出两倍的变化，映射到染色体3和13上的数量性状基因座，其中这些基因座显示出上位性相互作用。我们确定了潜在的遗传相互作用，由bHLH转录因子Neurog2介导，在染色体3基因座，在染色体13基因座处抑制LIM同源结构域转录因子Isl1。使用单和双条件敲除小鼠，我们确认了每个基因的反补贴作用，并在体外验证Isl1的5'UTR中两个单核苷酸多态性的关键作用，其中一个产生新的E-box，介导Neurog2的抑制作用。
