Reduced Glucose Consumption in the Curly Tail Mouse Does Not Initiate the Pathogenesis Leading to Spinal Neural Tube Defects

Manuscript received 7 November 1997. Initial reviews completed 20 March 1998. Revision accepted 18 May 1998.

Department of Anatomy and Embryology and ^* Department of Genetics, Faculty of Medicine, University of Maastricht, NL-6200 MD Maastricht, Netherlands

At embryonic stages of neural tube closure, the mouse embryo exhibits a high rate of glycolysis with glucose as the main energy source. In the curly tail mouse, often used as model system for study of human neural tube defects, a delay in closure of the posterior neuropore (PNP) is proposed to be indirectly caused by a proliferation defect in the caudal region. Because glucose is important for proliferation, we tested glucose uptake in curly tail and control embryos, and in a BALB/c-curly tail recombinant strain. The structure and expression of Glut-1, a glucose transporter molecule that is abundantly present during those embryonic stages and that has been mapped in the region of the major curly tail gene, were also studied; however, no strain differences could be demonstrated. Glucose uptake was determined by measuring glucose depletion from the medium in long-term embryo cultures that encompassed the stages of PNP closure and by measuring accumulation of ³H-deoxyglucose in short-term cultures at the stages of early and final PNP closure. Both approaches indicated a reduced glucose uptake by curly tail and recombinant embryos. Surprisingly, the uptake per cell appeared normal, accompanied by a significantly lower DNA content of the mutant embryos. Therefore, it is unlikely that reduced cell proliferation is caused by a reduction in glucose supply during the pathogenesis of the defects in curly tail embryos. The reduced DNA content as well as the reduced glucose uptake per embryo are likely downstream effects of the aberrant proliferation pattern.

The Journal of Nutrition Vol. 128 No. 10 October 1998, pp. 1819-1828
Copyright ©1998 by the American Society for Nutritional Sciences