Spontaneous ophthalmic lesions in young Sprague-Dawley rats.

Eight hundred eight Sprague-Dawley rats were examined for ophthalmic abnormalities during a pretest period in various preclinical safety assessment studies. Persistent pupillary membrane, corneal crystal, healed minor trauma, synechia, coloboma of the iris, lens luxation, cataract, persistent hyperplastic primary vitreous, vitreous hemorrhage, coloboma of the optic disc or choroid, remnant of hyaloid arterial system, retinal hemorrhage, retinal detachment, retinal folding and choroidal defect were observed. The incidences of corneal crystal, synechia, and nuclear cataract in this survey were higher than those reported previously. On the other hand, retinal folding in this survey was less common than that reported previously. These results suggest that background data of eye problems in albino rats should be accumulated in each own laboratory colony. In addition, since spontaneous eye problems are common in young albino rats, elimination of rats with ophthalmic abnormalities from study groups by an ophthalmic examination during a pretest period would facilitate to evaluate toxicity potential of test compounds in safety assessment studies.     

High incidence of chromophobe pituitary adenoma-like lesions in an inbred Sprague-Dawley breeding rat colony

A high incidence is recorded of pituitary chromophobe adenomalike lesions in an inbred Sprague-Dawley line of laboratory rats. 80 % of the males and 5 % of the females had the lesion at an age of about 340 days. The patho-anatomical features are described and the significance of the lesion is shortly discussed.     

Hermaphroditism in a Sprague-Dawley rat

A spontaneous case of unilateral true hermaphroditism was observed during the routine necropsy of a 9-week-old presumed female Sprague-Dawley rat on a repeat-dose toxicity study. There were no drug-related effects observed. True hermaphroditism is rare in rats, and despite the large numbers of rats examined annually, few cases are reported in the literature.     

Ameloblastic odontoma in a Sprague-Dawley rat

A spontaneously arising ameloblastic odontoma of the mandible is reported in in a 2-years old female Sprague-Dawley-rat. The morphological characteristics of the tumor are described as well as discussed in consideration of its histogenesis and differential diagnoses.     

Immunolocalization of ghrelin in the stomach of Sprague-Dawley rat

To investigate the distribution of ghrelin in different regions of stomach in Sprague-Dawley rat, and attempt to compare with those of humans and other mammalian species in this study, the stomach of rats was divided into five sections, cardia, fundus, greater curvature, lesser curvature and pylorus. Immunohistochemistry and Western blotting were performed to investigate the ghrelin-producing cells. The immunolocalization and protein levels of ghrelin differed significantly in different regions of stomach in rats. It was present at a high level in the greater curvature of the pars glandularis, and the lesser curvature. In the fundus and pylorus, no ghrelin immunoreactive cells were detected. In this study, we elucidated the distribution of ghrelin-producing cells in different regions of rat stomach in detail for the first time. It is further considered that the differences of ghrelin distribution in stomach of different species may induce different stimulatory effects on fat accumulation and metabolism.     

Spontaneous complex odontoma in a Sprague-Dawley rat

Complex odontoma from a female Sprague-Dawley rat is described histopathologically. Necropsy revealed a hard (bony), white mass (3.0 x 3.0 x 2.1 cm) on the left mandible. Microscopically, the mass consisted of islands or nests of epithelial and mesenchymal elements that formed abortive tooth structures. In other areas, tooth formation consisted of a pulp cavity lined by layers of odontoblasts, dentin, enamel, and ameloblasts. Concerning all features of normal tooth formation which was differentiated and mineralized yet completely disorganized, the diagnosis of complex odontoma was recommended.     

Granular cell lesions in the distal female reproductive tract of aged Sprague-Dawley rats

During the review of a rat carcinogenicity study, a spectrum of granular cell lesions was recognized in the distal female reproductive tract. To verify the diagnoses, cell populations of nine granular cell alterations of the cervix or vagina were characterized immunohistochemically and four were evaluated ultrastructurally. Immunoreactivity was demonstrated in 8/9 cases with S100 protein, 6/9 cases with neuron-specific enolase, and 7/9 cases with Leu-7. Granular cells were negative for smooth muscle-specific actin and calretinin. The immunohistochemical profile of these lesions was similar to that previously reported in other species, including humans. Ultrastructurally, as expected many lysosomal bodies were present in the cytoplasm of granular cells in all specimens evaluated. Based on the detailed evaluation of a series of lesions, we adopted the following diagnostic criteria and nomenclature for the granular cell changes of the female reproductive tract of rats. Granular cell aggregates were non-space-occupying lesions composed of clusters of typical granular cells. Benign granular cell tumors were space occupying lesions that typically contained prominent interstitial collagen and were either discrete masses or were difficult to discern from the surrounding tissues. Some benign tumors also contained foci of spindle cells with decreased granularity. Malignant tumors exhibited pleomorphism and an increased nucleus: cytoplasm ratio morphologically but had the same biologic behavior as the benign tumors. We applied these diagnostic criteria during the review of controls from 9 carcinogenicity studies. Up to 23% of control females in those carcinogenicity studies had granular cell lesions that could be classified into one of the three categories. Granular cell lesions appear to be common in the cervix/vagina of the Sprague-Dawley rat, and tumors may develop from granular cell aggregates.     

Rudimentary hemidesmosome formation in congenital generalized junctional epidermolysis bullosa in the Sprague-Dawley rat

Seven of 14 newborn pups in a litter of Sprague-Dawley rats were found to have generalized detachment of the epidermis, which was thin, wrinkled, and hung in loose folds over distal extremities. Histologic and ultrastructural examination of the skin showed noninflammatory separation of the epidermis from the dermis at the lamina lucida of the basement membrane zone. Ultrastructurally, hemidesmosomes were small and had a rudimentary appearance; keratin tonofilaments in basal keratinocytes were detached from the hemidesmosomes. The skin lesions were consistent with generalized junctional epidermolysis bullosa, which has not previously been reported in the rat. In humans, generalized junctional epidermolysis bullosa is most commonly caused by autosomal recessive inheritance of defective proteins of the hemidesmosomes or anchoring filaments. The specific protein defect involved in the rat lesion was not determined because fresh frozen tissue was not available.     

Evaluation of the Sprague-Dawley rat as a model for vertical transmission of Brucella abortus

Vertical transmission of Brucella abortus in Sprague-Dawley (SD) rats was verified with microbiologic, serologic, and polymerase chain reaction (PCR) methods. The 38 initially Brucella-free SD rats, weighing 200 to 250 g, were injected subcutaneously with 50 microL of a suspension containing 1 x 10(9) colony-forming units (cfu) of B. abortus biotype 1 Korean isolate. The rats were allowed to mate with uninfected SD rats. The isolate was detected by culture and by AMOS (abortus, melitensis, ovis, suis) PCR in testis tissue of infected male rats and splenic tissue of infected female rats. By 7 d after inoculation, the results of both the rose bengal test (RBT) and the plate agglutination test (PAT) were positive for antibody against B. abortus; the reciprocal antibody titre ranged from 200 to 400 in the 1-mo-old offspring and 800 in their dams. The infected rats directly transmitted Brucella to their breeding partners and offspring. Fetuses of infected dams were found to be infected at 20 d of gestation. These data are discussed in relation to a model for epizootic and zoonotic cases possibly involving wild animals. Additional rigorous experiments are warranted to explore the value of this model in developing measures to prevent congenital brucellosis.     

Effect of time of exposure to rat coronavirus and Mycoplasma pulmonis on respiratory tract lesions in the Wistar rat.

The effects of time of exposure on the progression of pulmonary lesions in rats inoculated with Mycoplasma pulmonis and the rat coronavirus, sialodacryoadenitis virus (SDAV) were studied, using six groups of 18 SPF Wistar rats (n = 108). Rats were inoculated intranasally as follows: Group 1, sterile medium only; Group 2, sterile medium followed one week later by 150 TCID50 SDAV; Group 3, sterile medium followed by 10(5.7) colony forming units of M. pulmonis; Group 4, SDAV followed one week later by M. pulmonis; Group 5, M. pulmonis followed one week later by SDAV; Group 6, M. pulmonis followed two weeks later by SDAV. Six rats from each group were euthanized at one, two and three weeks after the final inoculation. In a separate experiment, six additional animals were inoculated in each of groups 3, 5 and 6 (n = 18) and were sampled at five weeks after they had received M. pulmonis. Bronchoalveolar lavage and quantitative lung mycoplasma cultures were conducted on two-thirds of the rats. Histopathological examination and scoring of lesion severity were performed on all animals. Based on the prevalence and extent of histopathological lesions, bronchoalveolar lavage cell numbers, neutrophil differential cell counts and the isolation of M. pulmonis, the most severe disease occurred in the groups that received both agents. There was no significant difference in lesion severity between the groups receiving both agents other than in those examined during the acute stages of SDAV infection. Based on these results, it is evident that SDAV enhances lower respiratory tract disease in Wistar rats whether exposure occurs at one week prior to or at various intervals following M. pulmonis infections.     

Ganglioneuromas of the thyroid gland in a colony of Sprague-Dawley rats.

Ganglioneuromas of the thyroid gland of Sprague-Dawley rats were found in 7.2% of 698 rats used in two, 2-year oncogenicity bioassays. The incidence of the tumor was unrelated to treatment or sex. Of the 52 ganglioneuromas of the thyroid gland identified in 50 animals, 40 (80%) had coincident C cell proliferations in the same or contralateral lobe. Ganglioneuromas were contiguous or commingled with C cell proliferations in 63.5% of the cases. The ganglioneuromas consisted of large ganglion cells and, in a few cases, cells thought to be less differentiated neuronal precursors, in a matrix of neurites and Schwann cells. They grew, infiltrating and expanding in the thyroid parenchyma, and did not metastasize. Immunohistochemical staining for calcitonin, S-100 protein, and neurofilaments, as well as electron microscopy, were used to further characterize the tumors. The close association of ganglioneuromas with C cell tumors supports the theory of neural crest origin of C cells and provides a parallel to the association of ganglioneuromas and pheochromocytomas in the adrenal medulla. This is the first report of ganglioneuromas occurring in the thyroid gland or occurring as a common entity in any species.