Genome sequence of the ferret facilitates study of human respiratory disease

NIAID CEIRS | Research Publication Commentary

Peng X et al. The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease. Nat Biotechnol. 2014 Nov 17.

Animal models of human disease have long been important tools for the study of disease pathophysiology and to develop effective therapies. Ferrets (Mustela putorius furo) are an attractive small animal model for human influenza virus infection and transmission studies primarily because, unlike mice, they exhibit numerous clinical features associated with human disease, have similar lung physiology, and display similar patterns of viral binding receptors throughout their respiratory tract.

In this paper, Peng et al. released a preliminary annotated 2.41 gigabase genome sequence of M. putorius furo. An international team led by Dr. Michael Katze at University of Washington annotated this genome sequence using results of gene expression analyses and changes in response to infection with two strains of pandemic influenza virus and examined how closely cystic fibrosis disease progression in ferrets mirrors the human disease.

Ferrets were infected with either the H1N1 2009 A/CA/04/2009 or the reconstructed 1918 H1N1 A/Brevig Mission/1/1918 pandemic virus. Tissue samples were collected from both the trachea and lung at various time points post infection to analyze gene expression. RNA-Seq analysis of the samples revealed that transcriptional changes were more extensive in the trachea than in the lung, and the kinetics of gene expression changes differed by infecting viruses and tissue compartments. The results from this side-by-side comparison of the host response may explain the differing course of infection for the two pandemic influenza strains.

Separately, the researchers used microarray expression analysis to investigate cystic fibrosis disease progression in the lungs of CFTR-knockout ferrets (mutations in the CFTR gene cause cystic fibrosis in humans) and compared the results to human cystic fibrosis datasets. They found that the predominant gene pathways involved in cystic fibrosis inflammatory responses appear to be conserved between humans and ferrets. Overall, these data indicate that some of the disease processes responsible for the lung damage seen in cystic fibrosis begin very early in life.

In summary, Peng et al. created a ferret genome and transcriptome resource, which will enhance the utility of ferrets for the study of human respiratory diseases, such as influenza and cystic fibrosis. In addition, the high similarity in protein sequence and shared tissue expression patterns that were found between humans and ferrets suggest that the ferret could be used to study a broader array of human diseases.