Ferret Genome Could Hold Clues to Respiratory Diseases
In a breakthrough study, scientists have sequenced the ferret genome in an attempt to provide clues to respiratory diseases such as influenza and cystic fibrosis.
"The sequencing of the ferret genome is a big deal," Michael Katze, University of Washington (UW) professor of microbiology who led the research, said in a news release. "Every time you sequence a genome, it allows you to answer a wide range of questions you couldn't before. Having the genome changes a field forever."
Ferrets, small mammals belonging to the weasel family, are ideal animal models for studying human diseases because they share similar strains that infect us. In the same way that infections spread from human to human, they spread among ferrets.
Scientists at Broad Institute of MIT and Harvard, in collaboration with Katze and colleagues of UW, decided to sequence the genome of a domestic sable ferret, Mustela putorius furo. After using a technique called transcriptome analysis to identify all RNA in the ferret's genome, researchers could determine which cells respond when combating diseases like influenza and cystic fibrosis.
Looking at Influenza
Once they sequenced the whole ferret genome, researchers at the University of Wisconsin-Madision, led by Yoshihiro Kawaoka, exposed ferrets in a lab to reconstructed versions of two deadly viruses similar to influenza: the one that caused the so-called Spanish flu that killed 25 million people worldwide during a pandemic in 1918, and the swine-flu virus that became infamous in 2009-2010. (Scroll to read on...)
Samples were collected from the animals' trachea and lungs on the first, third and eighth day of the infection. Transcriptome analysis showed that both viruses affected the carnivores' tracheae differently, triggering a response at different points during the infection.
"The 1918 flu elicited a huge response on day one and that response was sustained," explained Xinxia Peng, a research assistant professor in the Katze lab. "The 2009 pandemic flu triggered a response that gradually grew over several days. They had very different trajectories."
In the lungs, however, gene transcription triggered by both viruses was roughly the same; yet still distinct from the response seen in the trachea.
"This side by side comparison reveals that the host response to these two viruses differs primarily in the trachea and may explain the course of infection," Peng said.
Understanding Cystic Fibrosis
In another part of the study, to better understand cystic fibrosis, researcher John Engelhard led a team from the University of Iowa in genetically engineering a ferret lacking the gene for a membrane protein called the cystic fibrosis transmembrane conductance regulator (CFTR). Defects in the CFTR gene are primarily responsible for acquiring cystic fibrosis, an inherited disease that affects a whopping 30,000 Americans.
By knocking out CTFR in ferrets and performing transcriptome analysis, Engelhardt's team could observe differences in gene expression over the course of the disease. Such changes were seen on the first day of infection and noticeably increased over the following 15 days.
"We found that there are transcriptional changes from day one, right out-of-the-gate, and many of the changes are very similar to those seen in humans," added Peng. "The findings suggest that some of the disease processes responsible for the lung damage seen in cystic fibrosis begin very early in life."
Better understanding genetic responses to influenza and cystic fibrosis can possibly reveal in more detail the mechanisms behind these respiratory diseases and how they persist in humans. The findings can also be applied to a broader set of diseases, including heart disorders and diabetes.
The study is published in the journal Nature Biotechnology.