Abstract
Rapid evolution in transgenic (Tg) mouse technology now permits cell-specific and temporal control of fluorescent cell-labeling and gene inactivation. Here, we discuss the principal strategies that have been utilized to target, label, and manipulate hepatic nonparenchymal cells, with emphasis on the utility of constitutive and inducible Cre-lox systems. We summarize key findings of studies employing Tg technology to target hepatic stellate cells, myofibroblasts, liver sinusoidal endothelial cells, and macrophages to illustrate the power of these approaches in identifying cell-specific molecular mechanisms critical to the pathophysiology of liver disease. Increasing adoption of Tg techniques will help to answer fundamental questions regarding the pathogenesis of hepatic diseases and provide the mechanistic rationale to allow identification of novel drug targets, ultimately translating into effective therapies for patients with liver disease. (Hepatology 2015;61:2091–2099)
Highlights
Rapid evolution in transgenic (Tg) mouse technology permits cell-specific and temporal control of fluorescent cell-labeling and gene inactivation
We summarize key findings of studies employing Tg technology to target hepatic stellate cells, myofibroblasts, liver sinusoidal endothelial cells, and macrophages to illustrate the power of these approaches in identifying cell-specific molecular mechanisms critical to the pathophysiology of liver disease
Conditional deletion of targeted genomic DNA sequences has become a standard approach, facilitating both interrogation of cell-specific gene function and detailed study of cell ontogeny through fate mapping. These techniques have revolutionized our ability to interrogate the roles of specific genes and cell lineages in a broad range of hepatic disease processes. We discuss how this burgeoning field is being harnessed to explore the myriad roles of hepatic nonparenchymal cells (NPCs) in the pathophysiology of liver disease
Summary
Citation for published version: Greenhalgh, SN, Conroy, KP & Henderson, NC 2015, 'Cre-ativity in the liver: Transgenic approaches to targeting hepatic nonparenchymal cells', Hepatology, vol 61, no. Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, known as Version of record
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