Genetically engineered mice have been induced to produce
live models that may enable them to better understand olfactory loss often seen
among sinusitis patients, by scientists at a Johns Hopkins laboratory.
The researchers say that their mouse models do not have one
key sense that is essential to tasting
food or sensing danger from foul odours.
They, however, add that this olfactory loss among the mice
"A sense of smell in good working order is essential to
our quality of life, and these genetically engineered mice give us the first
real animal model for better understanding, treating and preventing people from
suffering a loss of olfactory function due to sinonasal inflammation," says
sinusitis expert Dr. Andrew Lane,
who led the team that developed the olfactory-compromised mice.
"And because we can turn on and off the inflammation in
these mice, we really can mimic how the most overlooked and very disabling
aspect of sinusitis, the loss of smell, or anosmia, plays out in people,"
adds Lane, an associate professor at the Johns Hopkins University School of
On the significance of having live mouse models, Lane says:
"Until now, the lack of realistic animal models for each of the key
symptoms of chronic inflammation in the nasal tissue - such as the growth of
nasal polyps, the loss of the sense of smell, swollen sinus tissue, or clogged
and runny noses - has slowed sinusitis research and hindered our search for
He says that another key advantage to the new sinusitis
mouse is that it can be more easily studied than human olfactory tissue that is
surgically difficult to cut out from deep inside the skull, and sits
dangerously close to the brain.
To ensure that their the model worked, the researchers
induced sinusitis among the mice by mixing a drug in their water for nearly two
months, and tested samples of olfactory tissue weekly for any sense of smell in
response to various odours.
They found that the sense of smell, as gauged by minute
electrical currents in olfactory tissue, dropped progressively, by 50 percent
within two weeks, and stopped completely after six weeks.
Viewing the issue under microscope, the researchers observed
that white blood cells were visible, a telltale sign of inflammation. Olfactory
nerve cells had nearly disappeared.
However, when the researchers stopped the drug-induced
sinusitis, olfactory nerve cells rebounded and grew back within a couple of
weeks, "proving that what we have is a mouse with reversible olfactory
loss due to inflammation, which should speed up our learning more about the
disease and testing new therapies," says Lane.
"Ultimately, we hope to develop treatments that allow
the sense of smell to recover, even in the presence of a hostile inflammatory
environment due to sinusitis," Lane adds.
He says that in another phase of the research, other
anti-inflammatory drugs like infliximab (Remicade), which is used to treat
arthritis, will be tested to see whether they can spur growth of olfactory
neurons during sinusitis.
Lane also plans to add more sinusitis features to the animal
model, including progressive swelling of sinus tissue and rhinitis.