Why zebra finches don't get hypercholesterolemia.

In his 1994 classic, Why Zebras Don’t Get Ulcers , Robert Sapolsky (1) chronicles how the pathological effects of chronic stress commonly seen in humans are much rarer in nonhuman animals. A new paper by Velho et al. (2) in PNAS reports a fascinating discovery that provides an update to this theme. In this paper, the authors investigate the evolution of a receptor involved in cholesterol uptake by cells that is also exploited by the vesicular stomatitis virus (VSV) to enter cells during infection. They find that in songbirds—including the popular laboratory model, the zebra finch—this low-density lipoprotein receptor (LDLR) is missing several key exons found in many other avian groups as well as in mammals. This apparent case of evolutionary loss of function raises interesting questions about how songbirds manage to balance their cholesterol levels and avoid hypercholesterolemia (hence the title of this Commentary). This finding also has important implications for a variety of other fields, ranging from efforts to use VSV-G–pseudotyped lentiviruses as a tool to manipulate gene expression, to efforts to understand and control vesicular stomatitis, a major agricultural disease caused by VSV.\n\nNot surprisingly, the path to this fascinating discovery was far from straightforward. Songbirds represent important model organisms for the study of learned vocal communication because they, like humans but unlike typical laboratory mice or rats, are robustly capable of vocal imitation (3). To date, however, the genetic tools for testing candidate genes for learning processes have lagged behind those available in mice and rats. To address this gap, researchers have strived over many years to optimize viral transduction in zebra finches to test the functional effects of experimentally altered gene expression levels. Early forays focused on testing VSV-pseudotyped lentiviruses due to their high success rate in mammals and some birds including quail and chickens … \n\n[↵][1]1To whom correspondence may be addressed. Email: sawhite{at}ucla.edu or wright{at}nmsu.edu.\n\n [1]: #xref-corresp-1-1