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World J Stem Cells. Nov 26, 2014; 6(5): 571-578
Published online Nov 26, 2014. doi: 10.4252/wjsc.v6.i5.571
Connexin mutant embryonic stem cells and human diseases
Kiyomasa Nishii, Yosaburo Shibata, Yasushi Kobayashi
Kiyomasa Nishii, Yasushi Kobayashi, Department of Anatomy and Neurobiology, National Defense Medical College, Saitama 359-8513, Japan
Yosaburo Shibata, Fukuoka Prefectural University, Tagawa, Fukuoka 825-8585, Japan
Author contributions: All authors contributed to this paper.
Correspondence to: Kiyomasa Nishii, MD, PhD, Department of Anatomy and Neurobiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. nishii@ndmc.ac.jp
Telephone: +81-4-29951478 Fax: +81-4-29965186
Received: August 13, 2014
Revised: September 11, 2014
Accepted: September 16, 2014
Published online: November 26, 2014
Processing time: 46 Days and 2.2 Hours
Abstract

Intercellular communication via gap junctions allows cells within multicellular organisms to share small molecules. The effect of such interactions has been elucidated using mouse gene knockout strategies. Although several mutations in human gap junction-encoding connexin (Cx) have been described, Cx mutants in mice do not always recapitulate the human disease. Among the 20 mouse Cxs, Cx26, Cx43, and Cx45 play roles in early cardiac or placental development, and disruption of the genes results in lethality that hampers further analyses. Embryonic stem cells (ESCs) that lack Cx43 or Cx45 have made analysis feasible in both in vitro differentiated cell cultures and in vivo chimeric tissues. The success of mouse ESCs studies is leading to the use of induced pluripotent stem cells to learn more about the pathogenesis of human Cx diseases. This review summarizes the current status of mouse Cx disruption models and ESC differentiation studies, and discusses their implication for understanding human Cx diseases.

Keywords: Embryonic stem cells; Induced pluripotent stem cells; Gap junction; Human diseases; Genetic models; Differentiation; Chimera

Core tip: Numerous gap junction-encoding connexin (Cx) mutant mice have been established as models of human diseases. Although these analyses have facilitated current understanding of native Cx functions and the pathogenesis of related diseases, care must be taken when extrapolating findings from mice to humans, and vice versa, because there can be striking diversity in tissue organization and Cx expression patterns between these species. Recently, the use of human induced pluripotent stem cells (iPSCs) allowed further direct approaches for studying human diseases. According to the studies using mutant mouse embryonic stem cells, Cx mutant human iPSCs may become a useful model.