Breeding of CC06_ΔF508-/+ heterozygotes does not produce homozygotes mice CC06_ ΔF508-/-, indicating potential premature death in utero for this line. However, CC37_ ΔF508-/+ produces 10% of vital homozygotes mice CC37_ ΔF508-/-. These CF mice showed a significantly lower survival rate post-birth with reduced body weight in comparison to the congenic WT mice. Haematological analysis showed significantly higher neutrophil in CF than WT mice, indicating an ongoing systemic inflammation. Histopathology indicated that CF mice exhibit both the expected CF-related gut pathology and, different from previous models, alterations in the lungs. Bronchial epithelium of CF mice was diffusely hyperplastic with multiple-layers of epithelial and increased of goblet cells. Muco-obstructive alterations in the lungs were observed in the trachea and major bronchi of CF mice. Additional pathological phenotypes have been observed in other organs including pancreas, heart, reproductive tract, spleen, thymus and bone marrow. In conclusion, CC lines greatly expanded the range of disease phenotypes relative to classical inbred strains and may lead to the generation of disease specific mouse model that potentially reproduce the CF human disease.

Congress abstracts

– Sipione B, De Fino I, Viviani F et al. “New-genetically diverse mice to mirror complexity of cystic fibrosis respiratory infections“. 12th European CF Young Investigator Meeting, Paris (France), 21-23 February, 2018