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Science 310 (5748): 683-685

Copyright © 2005 by the American Association for the Advancement of Science

NPY/AgRP Neurons Are Essential for Feeding in Adult Mice but Can Be Ablated in Neonates

Serge Luquet, Francisco A. Perez, Thomas S. Hnasko, Richard D. Palmiter*

Abstract: Hypothalamic neurons that express neuropeptide Y (NPY) and agouti-related protein (AgRP) are thought to be critical regulators of feeding behavior and body weight. To determine whether NPY/AgRP neurons are essential in mice, we targeted the human diphtheria toxin receptor to the Agrp locus, which allows temporally controlled ablation of NPY/AgRP neurons to occur after an injection of diphtheria toxin. Neonatal ablation of NPY/AgRP neurons had minimal effects on feeding, whereas their ablation in adults caused rapid starvation. These results suggest that network-based compensatory mechanisms can develop after the ablation of NPY/AgRP neurons in neonates but do not readily occur when these neurons become essential in adults.

Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Box 357370, Seattle, WA 98195, USA.

Note added in proof: Two related papers (28, 29) were published online while this Report was under review. In both cases, the authors report that partial ablation of NPY/AgRP neurons results in smaller mice that eat less than controls do. The partial ablation is probably the consequence of gradual ablation or partial penetrance of transgene expression. Neither paper describes the starvation phenotype nor the neonatal compensation reported here.

* To whom correspondence should be addressed. E-mail: palmiter{at}u.washington.edu


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