Transplacental Uptake of Glucose Is Decreased in Embryonic Lethal Connexin26-deficient Mice

Abstract

Mice that harbor a targeted homozygous defect in the gene coding for the gap junctional protein connexin26 died in utero during the transient phase from early to midgestation. From day 10 post coitum onwards, development of homozygous embryos was retarded, which led to death around day 11 post coitum. Except for growth retardation, no gross morphological alterations were detected between homozygous connexin26-defective embryos and wild-type littermates.At day 9 postcoitum, when chorioallantoic placenta started to function, connexin26 was weakly expressed in the yolk sac epithelium, between syncytiotrophoblasts I and II in the labyrinth region of the placenta, and in the skin of the embryo. At day 10 post coitum, expression of connexin26 in the placenta was much stronger than at the other locations. To analyze involvement of connexin26 in the placental transfer of nutrients, we have measured embryonic uptake of the nonmetabolizable glucose analogue 3-O-[14C]methylglucose, injected into the maternal tail vein. At day 10 post coitum, viable, homozygous connexin26-defective embryos accumulated only ∼40% of the radioactivity measured in wild-type and heterozygous littermates of the same size. We conclude that the uptake of glucose, and presumably other nutrients as well, from maternal blood into connexin26-deficient mouse embryos was severely impaired and apparently not sufficient to support the rapid organogenesis during midgestation. Our results suggest that connexin26 gap junction channels likely fulfill an essential role in the transfer of maternal nutrients and embryonic waste products between syncytiotrophoblast I and II in the labyrinth layer of the mouse placenta.

Gap Junctions

“…In many of these cases, a given connexin occupies a particular niche, supplying an essential function that is not compensated by another connexin. For example, Cx26 deletion is embryonic lethal because of a disruption of glucose transport between syncytiotrophoblast I and II in the labyrinth layer of the placenta, which are coupled by gap junctions (Gabriel et al 1998). In contrast, the human placenta contains only one giant syncytiotrophoblast and so is not vulnerable to Cx26 mutations.…”

Modifications in Connexin Expression in Liver Development and Cancer

“…The predominant presence of Cx26 in this acinar region further substantiates the involvement of Cx26 signalling in hepatic growth. Whilst deletion of Cx26 results in embryonic lethality in mice (Gabriel et al, 1998), Cx32-defi cient mice show only subtle alterations, like decreased conduction velocity in sciatic nerve, increased growth rate of hepatocytes and an increase of chemically induced neoplastic lesions in the liver (Evert et al, 2002;Nelles et al, 1996;Ott et al, 2006;Temme et al, 1997). Nevertheless, in adult liver, gap junctions fulfi l a critical role in maintaining functional differentiation.…”

Role of gap junctions in epilepsy

“…Knockout of Cx43, the major astrocytic connexin, is neonatal-lethal [124] and causes neural crest migration deficits [125] . Deletion of Cx26 [126] or Cx45 [127] is also embryonic-lethal. With the application of conditional gene knockout techniques, especially the Cre-Lox recombination system, the roles of these connexin proteins in different brain cell types in epilepsy can be widely tested in the near future, and the functions of neuronal networks and astrocytic networks linked by their specific connexins can be distinguished under epileptic conditions.…”