Spontaneous Lung Lesions in Aging Laboratory Rabbits (Oryctolagus cuniculus)

Abstract

Spontaneous age-related lesions of laboratory rabbits are not well documented in the contemporary scientific literature. A retrospective study of diagnostic necropsies of 36 rabbits >2 years of age found a number of common lung lesions. Fibromuscular intimal hyperplasia affected medium and to a lesser extent large pulmonary arteries and was present to a variable extent in all 36 rabbits >2 years of age. The lesions were characterized by fragmentation and/or reduplication of the internal elastic lamina (IEL), proliferation of smoothelinþ/alpha-smooth muscle actin (a-SMA)þ/vimentinÀ smooth muscle cells and fewer smoothelinÀ/a-SMAþ/vimentinþ myofibroblasts, and intimal deposition of collagen without thrombosis, embolism, or evidence of pulmonary hypertension. Pulmonary emphysema, present in 30/36 rabbits, was characterized by the loss of alveolar septa; most affected rabbits did not have clinical signs of respiratory disease. In 8/13 rabbits of the inbred EIII/JC audiogenic strain, we identified a unique syndrome of granulomatous pneumonia containing hyaline brown to gray, globular to ring-like acellular material that was Alcian blue and periodic acid-Schiff positive. The material was immunoreactive for surfactant protein-A and had the ultrastructural appearance of multilamellar vesicles, suggesting a genetic defect in surfactant metabolism. Additionally, we found small benign primary lung tumors (fibropapillomas, 5 rabbits) not previously described. Other findings included heterotopic bone (5 rabbits), subacute to chronic suppurative bronchopneumonia, pyogranulomatous pneumonia with plant material, and pulmonary artifacts from barbiturate euthanasia solution.Although spontaneous background lesions of aging laboratory mice and rats are well documented and described, 7,9,19,23,31 there is less information on spontaneous lesions of aging laboratory rabbits. 14,15,21 In part this is because of the types of acute or relatively short-term studies for which rabbits are commonly used. In some cases where age-related lesions are described, such as spontaneous pulmonary emphysema, 42 other more recent references are contradictory, based apparently on the lack of additional confirmatory reporting. 4,8 Other spontaneous age-related lesions, such as unique intimal proliferations in the pulmonary arteries, are poorly documented in the English language literature, 20 and can resemble iatrogenic lesions caused by experimental manipulation. 27 While most rabbits used in research are outbred New Zealand White (NZW) or Dutch-belted stock, inbred rabbits strains do exist, including the audiogenic (EIII/JC) strain. The inbred III/J parent rabbit strain was originally developed at the Jackson Laboratory in 1932 by Dr Paul B. Sawin using NZW rabbits from Dr William Ernest Castle. The audiogenic (EIII/J) substrain was selected for a predisposition to sound-induced seizures by Dr Richard R. Fox in 1961. 13 The strain came to Penn State Hershey in 1988 from the National Cancer Institute. 37 Rabbits have been used as an induced experimental...

Not Just Uterine Adenocarcinoma—Neoplastic and Non-Neoplastic Masses in Domestic Pet Rabbits (Oryctolagus cuniculus): A Review

“…7,23,27,83 Additionally, small fibropapillomas have been described in a population of rabbits, all of which were older than 2 years, with a mean age of 4 years, and without Shope papilloma virus exposure. 20 Lesions were characterized by epithelial papilliform proliferation with a prominent fibrous stalk.…”

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Rabbit

“…Early foam cell accumulation to partly occlusive atheromatous plaques were observed in the larger lung arteries 28 . Unique proliferations are seen as age related changes in the pulmonary arteries of both sexes and can resemble iatrogenic lesions 177 . Genetically altered strains of the NZW rabbit such as the Watanabe rabbit (Watanabe heritable hyperlipidemia rabbit, WHHL) are also used extensively.…”

“…Comments: Cooper et al reported a congenital surfactant pneumonia in the audiogenic (EIII/JC) strain of rabbits 177 . This pneumonia was frequently grossly visible as irregular firm tan nodules in the cranioventral portions of lung lobes.…”

Proceedings of the 2018 National Toxicology Program Satellite Symposium

“…The next most popular choice, fibropapilloma (13%), was also not a preferred diagnosis of the INHAND rabbit coauthors. While similar lesions have been described as fibropapillomas in the lungs of aging rabbits (Cooper et al 2017), the rabbit INHAND coauthors do not see evidence that this is a neoplastic process. During the open discussion at the end of the talk, there was general agreement that this was a common, nonspecific response to pulmonary injury and should not be labeled as a neoplasm.…”