Ralph H. Johnson VA Medical Center
Green light: Glowing mice help advance research
Mice are a common fixture in many research laboratory settings, however, Ralph H. Johnson VA Medical Center’s research facility has one special mouse, with distinct characteristics, that is helping researchers make great strides in their analysis of respiratory disease, among other things.
This normally black mouse glows fluorescent green when exposed to a black light.
“These transgenic mice are ‘engineered’ through a process that crosses their genes with that of a type of jellyfish,” said Charleston VAMC’s Associate Chief of Staff for Research R. Amanda C. LaRue, Ph.D. “When the process is successful, almost every cell in the mouse’s body emits a green glow that we can then use as a marker to track the movements of the types of cells we are interested in – in our case, hematopoietic stem cells (HSC).”
LaRue and her research team irradiate recipient mice, essentially killing their current stem cells, and replace them with HSCs from the green donor mouse. This allows them to easily see where the cells travel and how they change and react in the body in order to better understand the lung disease, pulmonary fibrosis.
“Patients who have pulmonary fibrosis develop scar tissue in their lungs that inhibits normal lung function,” LaRue explained. “Because of the scarring, it becomes increasingly difficult for the patient to breathe and, unfortunately, there is no cure. At this time, the only way to restore lung function in those suffering from this disease is a lung transplant and patients often die waiting for this procedure.”
Though pulmonary fibrosis affects both Veteran and non-Veteran populations, this study is of particular interest to those who served in the Gulf War. Military members who were in theater during this conflict are at increased risk for the disease due to the sand, geological dust and other particles they regularly inhaled in the desert environment.
LaRue’s team simulates this same exposure in the mice with the green HSCs by putting the animals to sleep and then injecting silica particles directly into their lungs.
“The tiny silica crystals, which make up sand, have extremely sharp edges that, when inhaled, chafe the sensitive tissue inside the lungs each time the person takes a breath,” said LaRue. “What we’ve found through our research is that the body sends out cells called circulatory fibroblast precursors (CFP) when this happens. These cells originate from stem cells in the bone marrow and migrate to the lungs through circulation to become fibroblasts. Fibroblasts are cells that heal damage in the body, but in patients with pulmonary fibrosis, these cells ultimately end up creating tough scar tissue that limits the ability of the lungs to inflate and take in oxygen.”
Servicemembers who have recently served in the wars in Iraq and Afghanistan may also be at risk for pulmonary fibrosis after working in similar environments as their Gulf War predecessors. However, since there is often a significant time gap between exposure and diagnosis of the disease, sometimes 30 or 40 years, these younger Veterans may not see symptoms until they are in their 50s or 60s.
“Our goal is to really make some significant progress in finding alternative treatments for this disease,” LaRue said. “I don’t see these cells as inherently ‘good’ or ‘bad,’ they’re basically just doing a job. If we can develop an understanding of why they do what they do, then we can work on trying to influence the undesirable behaviors.”
There are two prescription drugs currently approved by the Food and Drug Administration for use in treating pulmonary fibrosis patients. LaRue hopes her research will shed some light on how to use these drugs more effectively to possibly target receptors and suppress the production of the problematic fibroblasts.
“I see all of this as my way of giving back,” said LaRue. “I come from a big military family and this research is how I can be involved in helping our Veterans and contribute to the big picture.”