By Ilan Zipkin
Staff Writer

Knockout mice have been hailed as a means for examining the effects of a single gene on an entire animal, with results applicable to human physiology. However, gene disruptions made in embryonic mice can be difficult to reconcile with pharmacology data from mature non-knockout animals, forcing researchers to wait for validation from clinical studies.

Knockout mice published last week for neuropeptide Y (NPY) receptors and a corticotropin releasing factor (CRF) receptor illustrate the contradictory results that can come from knockout studies.

The case against: NPY KO in obesity

Feeding behavior and weight management signaling pathways in mammals are complex and often interact with each other, and the obesity picture is still evolving. Last week two Nature Medicine papers using knockout mice cast doubt on the validity of neuropeptide Y (NPY) receptors as drug targets in obesity, which could affect at least four biotech programs.