A study of background lung lesions in a colony of specific pathogen free rats from weaning to 6-months of age

Background lung lesions in the laboratory rat have long been a frustrating and confounding issue for researchers. Reports of distinctive but poorly characterised lung lesions occurring in rats overseas prompted this study, which aimed to assess the baseline occurrence and progression of background lung lesions in rats maintained under specific pathogen free (SPF) conditions at a commercial rodent production facility in Australia. The study design incorporated 200 rats (100 Sprague Dawley and 100 athymic nude) that were maintained under SPF conditions (either isolator or barrier housing) before being euthanased at 3, 6, 12, 18 or 24 weeks of age. Two additional groups of 10 rats were housed within external facilities and euthanased at 12 weeks of age. During postmortem examination, gross lesions were recorded and lung samples were collected for microbiological culture and histopathology. A variety of microscopic and macroscopic lung lesions were identified within the study population. Where appropriate, classification and/or grading schemes were utilised or developed to further characterise these lesions. The most prevalent lesions were lymphohistiocytic interstitial pneumonia and perivascular inflammatory cell cuffing and prevalence of these lesions tended to increase with rat age, regardless of rat strain or housing type. There were no consistent trends in lesion prevalence across rat strain and housing type. The predominant combination of lesions was distinctive and compatible with descriptions of the disease known as “rat respiratory virus” and later, infectious interstitial pneumonia. Previously a poorly characterised entity of unknown aetiology, during the course of this study, Pneumocystis carinii was reported by others (Livingston, Besch-Williford et al. 2011, Henderson, Dole et al. 2012) to be the cause of this disease. Subsequently in the current study, histochemical staining demonstrated fungal organisms in a large proportion of affected athymic nude rats and P. carinii DNA was also detected in some rats via PCR assay. While there were minor differences in lesion progression and imperfect agreement between histopathologic lesions and PCR results, the results of this study are consistent with the recent literature outlining a causative role for P. carinii in this distinctive pneumonia in the rat