David, Catherine; (1992) The role of gap junctions in pre-implantation mouse development. A study of the DDK defective strain. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The aim of this work was to understand the basis of the defect in the mouse DDK strain. Defective embryos are produced when DDK females are mated with males of an alien strain (C3H). 95% of the DDK/C3H embryos are destined to decompact and fail to form normal blastocysts. A short review on gap junctions, followed by a discussion of mouse embryo pre-implantation development is presented in the Introduction. The morphology and the pattern of gap junctional communication in control and defective DDKembryos from the 8- to the 16-cell stage were compared. The results confirm that DDK/C3H embryos transfer Lucifer Yellow through gap junctions more slowly than controls. The physiological basis of the DDK syndrome was examined. Intracellular pH measurements indicate that 8-cell DDK/C3H embryos have significantly lower pHi than control embryos at the same stage. This could account for the reduction of dye transfer through gap junctions observed within the DDK/C3H population. Artifically lowering intracellular pH in normal 8-cell control embryos with butyrate for 4 hours reduced gap junctional communication and reproduced the DDK phenotype. Treatment with cyclic-AMP significantly speeded dye transfer in control and DDK/C3H embryos at the 8-cell stage. Preliminary experiments suggest that cyclic-AMP may rescue some DDK/C3H embryos to the blastocyst stage, but the effect is small (about 25%). Gap junctions were immunologically identified with a specific antibody to gap junction protein. The same protein was present in gap junctions of embryos from both control and defective strains. Since DDK/C3H embryos have functional gap junctional channels, the gap junction proteins themselves probably are not directly implicated in the DDK/C3H defect. It is more likely that defective pHi regulation is responsible. A general discussion and an hypothesis for the role of gap junctions is presented.

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