Voltage-dependant anion channels: novel insights into isoform function through genetic models.

Voltage-dependant Anion Channels, also known as mitochondrial porins, are pore-forming proteins located in the mitochondrial outer membrane (MOM) that, in addition to forming complexes with other proteins that localize to the MOM, also function as the main conduit for transporting metabolites between the cytoplasm and mitochondria. VDACs are encoded by a multi-member gene family, and the number of isoforms and specific functions of VDACs varies between species. Translating the well-described in vitro characteristics of the VDAC isoforms into in vivo functions has been a challenge, with the generation of animal models of VDAC deficiency providing much of the available information about isoform-specific roles in biology. Here, we review the approaches used to create these insect and mammalian animal models, and the conclusions reached by studying the consequences of loss of function mutations on the genetic, physiologic, and biochemical properties of the resulting models. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism.

Animal models of glycogen storage disorders.

Glycogen is a polymer of glucose needed to provide for a continuous source of glucose during fasting. Glycogen synthesis and degradation are tightly controlled by complex regulatory mechanisms and any disturbance in this regulation can lead to an inadequate reservoir of glycogen or an accumulation of excess or abnormal glycogen stored either in the cytosol or in the lysosomes. Problems in the degradation or synthesis of glycogen are referred to as glycogen storage disorders (GSDs), which individually are rare diseases, yet collectively are a major category of inborn errors of metabolism in humans. To date, 11 distinct forms of GSDs are represented in animal models. These models provide a means to understand the mechanisms that regulate and execute the synthesis and degradation of glycogen. In this review, we summarize animal models that have arisen spontaneously in nature or have been engineered in the laboratory by recombinant DNA techniques, and categorize the disorders of glycogen metabolism as disorders of either synthesis or degradation.