Gessler Manfred, Knobeloch Klaus-Peter, Helisch Armin, Amann Kerstin, Schumacher Nina, Rohde Elvira, Fischer Andreas, Leimeister Cornelia
Theodor-Boveri-Institute of the University of Wuerzburg, Physiological Chemistry I, Am Hubland, D-97074 Wuerzburg, Germany.
Curr Biol. 2002 Sep 17;12(18):1601-4. doi: 10.1016/s0960-9822(02)01150-8.
Gridlock (grl) is one of the first mutations characterized from the large zebrafish mutagenesis screens, and it results in an arterial (aortic) maturation defect, which was proposed to resemble aortic coarctation, a clinically important human malformation. While the grl mutation appears to be a hypomorph, grl knockdown experiments have shown even stronger effects on arterial development. We have generated a knockout of the murine Hey2 (gridlock) gene to analyze the mammalian phenotype. Surprisingly, Hey2 loss does not affect aortic development, but it instead leads to a massive postnatal cardiac hypertrophy with high lethality during the first 10 days of life. This cardiomyopathy is ameliorated with time in surviving animals that do not appear to be manifestly impaired during adult life. These differences in phenotypes suggest that changes in expression or function of genes during evolution may lead to quite different pathological phenotypes, if impaired.
Gridlock（grl）是大型斑马鱼诱变筛选中最早鉴定出的突变之一，它会导致动脉（主动脉）成熟缺陷，这种缺陷被认为类似于临床上重要的人类畸形——主动脉缩窄。虽然grl突变似乎是一种亚效等位基因，但grl基因敲低实验显示其对动脉发育的影响更强。我们通过敲除小鼠Hey2（gridlock）基因来分析其哺乳动物表型。令人惊讶的是，Hey2缺失并不影响主动脉发育，反而会导致出生后严重的心脏肥大，并在出生后的前10天内具有高致死率。在成年期似乎没有明显受损的存活动物中，这种心肌病会随着时间的推移而改善。这些表型差异表明，进化过程中基因表达或功能的变化如果受损，可能会导致截然不同的病理表型。
