Genetic evidence that glycolysis is necessary for gastrulation in the mouse.

Mouse embryos homozygous for the Gpi1-sa-m1H null allele (abbreviated to m) of glucose phosphate isomerase (GPI) die early in development. A histological study was undertaken to identify the earliest abnormalities attributable to the absence of this glycolytic enzyme. Two groups of embryos were produced and examined histologically from E6.5 to E9.5 days. Experimental embryos were produced by crossing heterozygous Gpi1-sa/m females with heterozygous Gpi1-sb/m males and compared with control embryos produced by crossing heterozygous Gpi1-sb/Gpi1-sb males. The first sign of abnormality attributable to homozygous m/m embryos appeared at 7.5 days when 32.2% of the embryos in the experimental group were histologically abnormal or retarded, compared to 8.3% in the control group. The putative homozygous m/m embryos had a range of abnormalities, but consistently the egg cylinder failed to be divided into the three cavities characteristic of normal 7.5-day embryos. This suggests that a deficiency in extraembryonic mesoderm formation resulted in the failure to form the amnion or chorionic mesoderm. At 8.5 and 9.5 days the abnormal embryos from the experimental cross had progressed little further. It is suggested that in the absence of GPI, energy production is impaired so that the embryo fails to develop beyond the egg cylinder stage and gastrulation has begun completed. Developmental failure may occur before gastrulation or once gastrulation has begun and produced some mesoderm. It is concluded that glucose phosphate isomerase and presumably, therefore, glycolysis is needed for normal gastrulation of mouse embryos.