Chapter 23: 'Negative' Physiology: What Connexin-Deficient Mice Reveal about the Functional Roles of Individual Gap Junction Proteins

Publisher Summary The molecular biological revolution has affected the studies of gap junctions for only about a dozen years. During this time, gap junction channels have been shown to be encoded by a family of connexin genes, and properties of these channels have been characterized in the mammalian cell lines and in Xenopus oocyte expression systems. Mutagenesis has begun to identify functional gating domains, and surprisingly common human genetic diseases have been associated with coding and noncoding region mutations in genes encoding several of the connexins. The newest approach, and the one emphasized in this chapter, consists of the evaluation of tissue and organ functions in mice in which the expression of individual connexin genes has been disrupted by homologous recombination [so-called gene “knockout” (KO) mice]. The chapter briefly discusses what the transgenics have expressed so far, emphasizing physiological studies carried out in the animals and in tissue culture, where properties of intercellular channels can be studied in detail. The extensive characterization of cellular, tissue, and organ alterations in these and other connexin knockout mice still have a long way to go before their phenotypes are totally understood. But such studies already demonstrate the impact that genetic manipulation has had on the field so far, and also highlight why it is currently so much fun to be a physiologist.