Gene therapy restores feeding behavior to starving mice

June 22, 2001 -- Researchers have used gene therapy to rejuvenate feeding behavior in starving mice. The genetically engineered mice had avoided eating because their brains contained a low level of dopamine.

The scientists experiments, which were reported in the June 2001 issue of the journal Neuron, provide new information about a region of the brain that helps integrate internal hunger signals and external sensory information about food to trigger feeding behavior.

A research team led by Richard D. Palmiter, a Howard Hughes Medical Institute investigator at the University of Washington, demonstrated that gene therapy restored dopamine production in specific areas of the brains of mutant mice. The mice, which were developed by Qun-Yong Zhou in Palmiters laboratory in the mid-1990s, lack tyrosine hydroxylase, an enzyme that is required to produce L-DOPA, a chemical precursor that is converted into the neurotransmitter dopamine. These mice lack the motivation to feed, and die of starvation a few weeks after birth, unless they are hand-fed or injected daily with L-DOPA. The gene therapy restored feeding behavior in the mice.

These dopamine-deficient mice have many other behavioral deficits, said Palmiter. In addition to not eating adequately, they show no preference for sweets, they fail to build nests and they lack curiosity in novel environments. They are generally hypoactive, they are also slow to initiate movements and they have difficulty with coordination -- a syndrome that resembles parkinsonism.

According to Palmiter, researchers did not know which region of the brain was responsible for the impaired feeding behavior and other deficits noted in the mice. Palmiter and his colleagues suspected that dopamine-producing neurons in the mid-brain

Contact: Jim Keeley
Howard Hughes Medical Institute

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