Rescue of Oogenesis in Cx37-null Mutant Mice by Oocyte-specific Replacement with Cx43

Mammalian oocytes and surrounding granulosa cells are metabolically coupled via gap junctions. In growing follicles of the mouse, gap junctions between oocytes and granulosa cells are assembled from connexin 37 (Cx37, encoded by Gja4), whereas those between granulosa cells are assembled from connexin 43 (Cx43, encoded by Gja1). This spatial separation, and the different permeability properties of gap junctions composed of Cx37 and Cx43, suggests that Cx37 channels serve a unique function in oogenesis. Female mice lacking Cx37 are sterile because oocytes do not complete their development. To test the hypothesis that the unique properties of Cx37 make it irreplaceable in oocytes, Cx43 was ectopically expressed in growing oocytes lacking Cx37. Transgenic mice were produced in which Gja1 is expressed in oocytes under control of the Zp3 (zona pellucida protein 3) gene promoter. When the transgene was crossed into the Cx37-null mutant line, oocyte-granulosa-cell coupling, oocyte growth and maturation, and fertility were all restored. Thus, despite their different properties, Cx43 is physiologically equivalent to Cx37 in coupling oocytes with granulosa cells.