Objective: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease which is usually diagnosed when irreversible lung damages already occurred. To date, little is known about the disease development before clinical manifestation. Recently, we developed a mouse model with conditional Nedd4-2 deficiency (Nedd4-2^-/-) that produces a spontaneously progressive IPF-like disease which offers the opportunity for studies from the initiating event to terminal lung disease.
Methods: We used in vivo and post mortem µCT imaging at different stages of IPF-like disease in conditional Nedd4-2^-/- mice and applied a µCT based fibrosis score to quantify consolidations, honeycombing-like-lesions, fissural thickening, peripheral bronchiectasis, parenchymal lines, and reticulations. Further, we used in vivo longitudinal scans to study disease development in individual mice.
Results: In vivo µCT imaging revealed the first fibrotic lesions 3 months after conditional Nedd4-2 deletion which further increasd in number and size the following months. In high resolution post mortem µCT scans, we found that unspecific interstitial alterations were detectable even at early stages of fibrotic lung disease, whereas IPF key features such as honeycombing-like-lesions develop late in disease progression.
Conclusion: By µCT imaging, we were able to demonstrate the development of IPF key features in conditional Nedd4-2^-/- mice and monitor disease progression of IPF like disease in vivo. Finally conditional Nedd4-2^-/- mice are a valuable tool to investigate new diagnostic markers and evaluate new therapeutic strategies for IPF.