Ciliopathies are a group of human genetic disorders caused by abnormalities with the formation or function of cilia, which are hair-like structures on the surface of cells.
Since they’re found on many types of cells, cilia affect various functions, including sensory perception, movement, and cell signaling. Damage to cilia as a result of genetic mutation can cause kidney and liver cysts, extra digits, obesity, blindness, and loss of hearing or smell in mammals.
To repair problems with cilia on olfactory neurons, a team led by Jeffrey Martens at the University of Michigan in Ann Arbor created some mutant mice.
First, they found a mutation in Intraflagellar Transport Protein 88 (IFT88) that’s associated with human ciliopathies, such as polycystic kidney disease. In people, this causes impaired growth, extra digits, blindness, and brain abnormalities.
Mice who are deficient in this protein have shorted and malformed cilia on neurons within the nose and can’t perceive odors; they’re called Oak Ridge polycystic kidney (ORPK) mice, and they die by early adulthood. So the researchers injected a functional IFT88 protein into the nose of these mutant mice.
They found that with gene therapy, newborn mice were better at suckling and feeding – behaviors associated with smell and olfactory function in mice.
ORPK mice are usually one-quarter the size of normal mice by three weeks of age, but treated pups showed a 60% increase in body weight.
In people, the accessibility of olfactory neurons would be an advantage in translating these results to the clinic, Nature explains. Gene therapy could be delivered by a simple injection or even a nasal spray.
The work was published in Nature Medicine last week.
[Via Nature News]
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