Connexin mutant embryonic stem cells and human diseases

Area of Science:

• Cellular Biology
• Genetics
• Developmental Biology

Background:

• Intercellular communication through gap junctions is vital for multicellular organisms.
• Mouse gene knockout models are used to study connexin (Cx) functions, but human disease relevance can be limited.
• Certain connexin gene disruptions in mice lead to embryonic lethality, hindering detailed analysis.

Purpose of the Study:

• To review the current status of mouse connexin (Cx) disruption models.
• To discuss the utility of mouse embryonic stem cell (ESC) differentiation studies for analyzing Cx functions.
• To explore the implications of these models for understanding human connexin diseases.

Main Methods:

• Analysis of existing mouse gene knockout strategies for connexins (Cxs).
• Utilizing mouse embryonic stem cells (ESCs) lacking specific Cx genes (e.g., Cx43, Cx45) for in vitro and in vivo studies.
• Reviewing studies employing induced pluripotent stem cells (iPSCs) for human Cx disease research.

Main Results:

• Mouse models for Cx26, Cx43, and Cx45 are lethal, complicating research.
• Cx-deficient ESCs enable feasible in vitro differentiation and in vivo chimeric tissue analysis.
• Induced pluripotent stem cells (iPSCs) are emerging as a tool for studying human Cx diseases.

Conclusions:

• Mouse ESCs offer a valuable platform for studying connexin functions and diseases.
• These models, including iPSC-based approaches, are crucial for elucidating the pathogenesis of human Cx disorders.
• Further research using these advanced models will enhance our understanding of connexin biology and disease.