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Multifocal retinal dysplasia in the Syrian hamster LAK:LVG (SYR).

Multifocal retinal dysplasia was diagnosed clinically in twenty-four of twelve hundred (2.0% incidence) LAK:LVG (SYR) Syrian Hamsters. The affected hamsters were part of twelve hundred animals to be used in oncogenic studies. Ther dysplastic retina were detected during ophthalmoscopic examinations of hamsters as young as 6 weeks and as old as 9 months. Ophthalmoscopically, the dysplastic foci varied from retinal streaks, sometimes called vermiform, to small, generally circular areas of cream-colored depigmentations. Blindness or othe apparent visual defects were not seen nor were the dysplasias associated with a generalized syndrome of disease. Histologic examination of the affected hamsters revealed focal dysplasias limited to the retina and were manifested as invaginations and rosette-like structures composed of elements of the photoreceptor layer, outer limiting membrane and outer nuclear layer. This paper describes the first incidence of a congenital retinal dysplasia found in an outbred strain of Syrian Hamster LAK:LVG (SYR), and correlates the ophthalmoscopic appearance and histopathology. In addition, a procedure for maintaining prolonged mydriasis for funduscopic photography is presented.

Animals↗

Criteria for development of animal models of diseases of the respiratory system: the comparative approach in respiratory disease model development.

Advances in the understanding of human respiratory disease can come from careful clinical studies of the diseases as they occur in man, but such studies are naturally limited in terms of experimental manipulation. In the last 2 decades, an increasingly complex plethora of experimental respiratory disease models has been developed and utilized by investigators, but relatively less attention has been paid to the naturally occurring pulmonary diseases of animals as potential models. This paper is aimed at presenting selected examples of spontaneous pulmonary disease in animals that may serve as exploitable models for human chronic bronchitis, bronchiectasis, emphysema, interstitial lung disease, hypersensitivity pneumonitis, hyaline membrane disease, and bronchial asthma. Chronic bronchitis in dogs is characterized by chronic cough, excessive mucus production, and chronic inflammatory changes in bronchial walls. The disease affects mainly smaller-breed dogs of middle age or older. Equine chronic bronchitis tends to be a small airway disease with marked goblet cell proliferation and excessive mucus production, which may be accompanied by alveolar emphysema. Many animals develop bronchiectasis or bronchiolitis obliterans secondary to chronic suppurative bronchopneumonia, but chronic respiratory disease (CRD) of rats may be the most useful model of bronchiectasis. Models for emphysema must include actual alveolar destruction and ideally should be accompanied by appropriate pathophysiologic decrements. Many animals occasionally develop emphysema, but the disease has not been well documented, except possibly in horses. The interstitial lung diseases of man represent a complicated and poorly understood group of entities and near-entities. The same is true for animals, although interstitial lung disease in animals is much less common than bronchopneumonia. Cattle seem prone to develop interstitial lesions. Proliferative interstitial pneumonia of cattle includes many morphologic similarities to the spectrum of human interstitial pneumonitides. Fibrosing alveolitis of cattle is a morphologic end point that may have its origins in different forms of interstitial injury. Hypersensitivity pneumonitis has been best detailed in cattle and in horses and is clinically, etiologically, immunologically, and morphologically similar to the disease in man. Hyaline membrane disease has been poorly documented in animals, with the possible exception of the neonatal respiratory distress syndromes of foals and piglets. Bronchial asthma is similarly not well established as a spontaneous disease in animals, although experimental models exist. Eosinophilic bronchiolitis of cattle may represent a useful asthma model but has been poorly detailed. In order to make them useful as models, more attention should be paid to detailing the clinical, morphologic, and etiologic aspects of these naturally occurring animal pulmonary diseases.

Animals↗

Efficacy of a temperature-sensitive Sendai virus vaccine in hamsters.

A temperature-sensitive HVJ-pB strain of parainfluenza type 1 (Sendai) virus was obtained from a persistently virus-infected cell culture. Intranasal inoculation of Syrian hamsters with the HVJ-pB temperature-sensitive mutant resulted in an abortive infection but induced a specific antibody response against Sendai virus without appreciable lesions in the respiratory tract. Prior exposure to the temperature-sensitive mutant protected hamsters from subsequent challenge with virulent wild-type virus. The efficacy of protection became apparent at 5 days after vaccination and lasted for at least 720 days. For practical use of the HVJ-pB vaccine, a single intranasal administration to newborn babies aged over 15 days is recommended.

Administration, Intranasal↗

Pseudotuberculosis in the Antwerp Zoo.

During the last five years (1970-1974) 42 cases of pseudotuberculosis were diagnosed among the Antwerp Zoo animals. The prevalence of disease, and the distribution frequency of gross lesions in the visceral organs were studied. The susceptibility of different animals and the influence of some factors to the disease are discussed. It demonstrates that Y. pseudotuberculosis, and particularly its two serotypes I and II, constitutes the principal causative agent. Pseudotuberculosis is found to be highly prevalent in cold season.

Animals↗

Exocrine pancreatic insufficiency syndrome in CBA/J mice. Ultrastructural study.

The pathogenesis of a spontaneously occurring exocrine pancreatic insufficiency (EPI) syndrome in CBA/J mice was studied at the ultrastructural level. Initial cytologic manifestations of this syndrome are seen as a progressive digestion of the zymogen granules, beginning at the periphery and proceeding toward the granule interior. Granule membrane breakdown, fusion of neighboring granules, and a release of zymogen contents into the cytoplasm are frequently observed in later stages; in some cases the entire granule contents appear digested before membrane breakdown is observed. In either case, pathologic changes are subsequently observed in mitochondria and rough endoplasmic reticulum. Remnants of lysed cells are then engulfed by invading macrophages, and infiltration by fat cells is observed. Secretory ducts and islets of Langerhans show no pathologic changes even after total autolysis of the exocrine pancreas. Morphologic evidence showing zymogen granule destabilization, coupled with biochemical evidence presented in an accompanying paper, indicate that intracellular autodigestion is the mechanism of exocrine cell death.

Animals↗

Myopathy in guinea pigs.

Myopathy resembling nutritional muscular dystrophy occurred in a colony of 150 guinea pigs. Of 54 animals affected, 27 died. Major clinical signs were depression, conjunctivitis, and reluctance to move. Lesions were widespread throughout skeletal and cardiac musculature. Clinical signs and deaths ceased when the diet was changed to a different commercial ration. A single intramuscular injection of sodium selenite and alphatocopherol brought prompt remission of clinical signs in one group of 20 so treated.

Animal Feed↗

The pathology of the Mongolian Gerbil (Meriones unguiculatus): a review.

Both naturally occurring disease processes and experimental models of human disease in the Mongolian gerbil were reviewed. The gerbil was highly susceptible to cerebral infarction following unilateral ligation of one common carotid artery and was useful in studies of the pathogenesis of stroke. Spontaneous epileptiform seizures mimicked those of human idiopathic epilepsy, and both seizure-sensitive and resistant strains have been bred. Perhaps because of its more efficient nephron, the gerbil accumulated four to six times as much renal lead as the rat, and the gerbil has been proposed as an experimental model of lead nephropathy. On standard diets, about 10% of the animals became obese, and some showed decreased glucose tolerance, elevated serum immunoreactive insulin and diabetic changes in the pancreas and other organs. Some breeders exhibited hyperactivity of the adrenal cortex associated with hyperglycemia, hyperlipidemia and degenerative vascular disease. Although dietary supplements of cholesterol were toxic and did not induce atherosclerosis, the gerbil was useful in other studies of cholesterol absorption and metabolism. Spontaneous, insidious periodontal disease became evident after about 6 months on standard diets, and dental caries were induced by cariogenic diets or by pathodontic streptococci. Spontaneous neoplasia occurred in 8.4--24% of gerbils, usually after 2 years of life. Adrenal cortical, ovarian and cutaneous tumors were the most consistently reported neoplasms.

Adrenocortical Hyperfunction↗

Cloning and characterization of cDNAs encoding a candidate glycogen storage disease type 1b protein in rodents.

Glycogen storage disease type 1 (GSD-1) is a group of genetic disorders caused by a deficiency in the activity of the enzyme glucose-6-phosphatase. (G6Pase). GSD-1a and GSD-1b, the two major subgroups, have been confirmed at the molecular genetic level. The gene responsible for GSD-1b maps to human chromosome 11q23 and a candidate human GSD-1b cDNA that encodes a microsomal transmembrane protein has been identified. In this study, we show that this cDNA maps to chromosome 11q23; thus it is a strong candidate for GSD-1b. Furthermore, we isolated and characterized candidate murine and rat GSD-1b cDNAs. Both encode transmembrane proteins sharing 93-95% sequence homology to the human GSD-1b protein. The expression profiles of murine GSD-1b and G6Pase differ both in the liver and in the kidney; the GSD-1b transcript appears before the G6Pase mRNA during development. In addition to G6Pase deficiency, GSD-1b patients suffer neutropenia, neutrophil dysfunction, and recurrent bacterial infections. Interestingly, although the G6Pase mRNA is expressed primarily in the liver, kidney, and intestine, the GSD-1b mRNA is expressed in numerous tissues, including human neutrophils/monocytes.

Adult↗

Expression of the Huntington disease gene in rodents: cloning the rat homologue and evidence for downregulation in non-neuronal tissues during development.

Huntington's disease (HD) is associated with an expanded and unstable (CAG) > 35 repeat within a gene of unknown function. We isolated the complete coding region of the rat HD gene (rhd) from cDNA libraries and investigated its expression in different developmental stages of rodent tissues. The rat gene exhibits 90% peptide sequence identity to the human and 96% to the murine sequence. The (CAG)n repeat is markedly reduced in the rat compared to the average human (CAG)n block. Northern blot analysis and in situ hybridizations reveal that in rodents the hd gene is already expressed during embryonal development. As in humans, the rhd gene is expressed in two transcriptional isoforms which result from different polyadenylation signals. In mice, however, a third transcript of intermediate size was found predominantly expressed in brain. This transcript is downregulated in later development. At day 14.5 p.c. the level of rhd expression is similar in the brain and in non-neuronal tissues. In contrast, the expression in non-neuronal tissues is markedly reduced in adult animals and corresponds to the restricted distribution of neuropathologic changes observed in HD patients.

Amino Acid Sequence↗