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NIH-funded researchers restore sense of smell in mice using genetic technique
Date:9/2/2012

e University of Michigan, Ann Arbor, and Jeremy C. McIntyre, Ph.D., a post-doctoral fellow in Martens' laboratory, worked with a mouse model carrying a mutation in the IFT88 gene. The mutation causes a decrease in the IFT88 protein, which leads to a dramatic reduction in cilia function in several different organ systems, including the olfactory system.

The researchers used an adenovirus to introduce a healthy copy of the gene as a way to restore IFT88 protein levels in the mice. They wanted to see if the reintroduction of the lost protein could restore cilia to the olfactory sensory neurons and return the ability to smell. For three consecutive days, the mice received intranasal gene delivery therapy and then were allowed 10 days for the infected sensory neurons to express the viral-encoded IFT88 protein. After that time, the mice were tested with increasing concentrations of an odorant (amyl acetate). Their responses were measured at the cellular, tissue, and synaptic levels, which all indicated that the mice had regained olfactory function.

"By restoring the protein back into the olfactory neurons, we could give the cell the ability to regrow and extend cilia off the dendrite knob, which is what the olfactory neuron needs to detect odorants," said McIntyre.

The change in olfactory function also has implications in the feeding behavior of the mice. The mouse model the scientists used is born underweight and its anosmia interferes with the motivation to eat, which in many mammals, including humans, is driven by smell. Treatment with adenovirus therapy increased bodyweight by 60 percent in treated compared to untreated mice, indicating that the restored olfactory function was motivating feeding.

The researchers plan to continue their work by developing another mouse model to look at the impact on olfactory function and the potential for restoring function when the IFT88 gene is completely missing, rather than just mutate
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Contact: Robin Latham
lathamr@nidcd.nih.gov
301-496-7243
NIH/National Institute on Deafness and Other Communication Disorders
Source:Eurekalert

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