title: Peripheral lymphangiogenesis in mice depends on ectodermal connexin-26 (Gjb2).
abstract: In order to study the specific function of connexin-26 (Cx26, also known as gap junction beta-2 protein; Gjb2), we generated knockin mice that expressed either a floxed lacZ reporter or, after Cre-mediated deletion, connexin-32 (Cx32)-coding DNA, both driven by the endogenous Cx26 promoter. Heterozygous Cx26knock-inCx32 (Cx26KICx32) embryos developed normally until embryonic day 14.5 but died before birth with severe lymphedemas. Although the jugular lymph sacs were normally developed, these embryos had a strongly reduced dermal lymphatic capillary network. By analyses of β-galactosidase reporter protein expression and lymphatic or blood endothelial-specific marker proteins, we demonstrated that Cx26 expression is temporally closely linked to lymphangiogenesis. No obvious phenotypic abnormalities were observed in Cx26KICx32 mice when Cre-mediated recombination was directed to mesenchyme or blood endothelium using the Prx1-Cre or Tie2-Cre mouse strains, respectively. By contrast, keratin-5-Cre-mediated replacement of Cx26 with Cx32 or deletion of both Cx26 alleles revealed severe lymphedemas similar to the general Cx26KICx32 phenotype. Thus, conditional ablation of Cx26 (loss of function) in ectoderm leads to partial disruption of lymphatic capillaries and embryonic death. We conclude that appropriate development of dermal lymphatic vessels in mice is dependent on the expression of Cx26 in the ectoderm.
authors.affiliation: Institute of Genetics, Division of Molecular Genetics, University of Bonn, 53117 Bonn, Germany.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Dicke
authors.forename: Nicole
authors.initials: N
authors.lastname: Pielensticker
authors.forename: Joachim
authors.initials: J
authors.lastname: Degen
authors.forename: Julia
authors.initials: J
authors.lastname: Hecker
authors.forename: Oliver
authors.initials: O
authors.lastname: Tress
authors.forename: Tobias
authors.initials: T
authors.lastname: Bald
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gellhaus
authors.forename: Elke
authors.initials: E
authors.lastname: Winterhager
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
mesh_terms: D000818:Animals; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004475:Ectoderm / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D055879:Gene Knock-In Techniques; D005818:Genetic Engineering; D018398:Homeodomain Proteins / Q000235:genetics; D042583:Lymphangiogenesis / Q000235:genetics; D042601:Lymphatic Vessels / Q000196:embryology* / Q000473:pathology; D008209:Lymphedema / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D042787:Receptor, TIE-2
chemical_list: D017630:Connexins; C000607043:Gjb2 protein, mouse; D018398:Homeodomain Proteins; C489936:Prrx1 protein, mouse; D000072259:Connexin 26; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse