Connexin31-deficiency in mice causes transient placental dysmorphogenesis but does not impair hearing and skin differentiation

Mutations in the human GJB3 gene that codes for Connexin31 (Cx31), a protei n subunit of gap junction channels, have recently been reported to cause de afness and the skin disorder erythrokeratodermia variabilis. To study the f unction of this gene in mice, we generated animals with targeted replacemen t of the Cx31 gene (Gjb3) by a lacZ reporter gene. Although homozygous Cx31 -deficient adult mice (Gjb3(-/-)) were found among the offspring of heteroz ygous Cx31-deficient parents (Gjb3(+/-)), 60% of the animals expected accor ding to Mendelian inheritance were lost between ED 10.5 and 13.5. Placentas of Gjb3(-/-) embryos at ED 9.5 were smaller than controls as a result of s everely reduced labyrinth and spongiotrophoblast size. From ED 10.5 onward, placentas of surviving Gjb3(-/-) embryos recovered progressively and reach ed normal size and morphology by ED 18.5. This corresponds to a time period in which another connexin isoform, Connexin43, is upregulated in spongiotr ophoblast cells of Cx31-deficient and control placentas. No morphological o r functional defects of skin or inner ear were observed in surviving adult Gjb3(-/-) mice. We conclude that Cx31 is essential for early placentation b ut can be compensated for by other connexins in the embryo proper and adult mouse. (C) 2001 Academic Press.