The FVB/N mouse strain was created in the early 1970s and has since been used extensively in transgenic research because of its well-defined inbred background, superior reproductive performance, and prominent pronuclei of fertilized zygotes, which facilitate microinjection of DNA. Little is known, however, about the survivability and spontaneous disease of nontransgenic FVB/N mice. Therefore, the purpose of this study was to determine survival to 24 mo of age and the incidence of neoplastic and nonneoplastic disease at 14 and 24 mo of age. At 14 mo of age, the incidence of tumor-bearing mice was 13% in males (n = 45) and 26% in females (n = 98).
In order to evaluate a short-term carcinogenicity testing system using CB6F1 -Tg rasH2 (rasH2-Tg) mice carrying a human prototype c-Ha-ras gene, 26-week studies were conducted in 12 different facilities as a part of an International Life Science Institute Health and Environmental Science Institute (ILSI HESI) international collaborative project. In each study N-methyl-N-nitrosourea (MNU) was administered to a separate group of rasH2-Tg mice by single intraperitoneal injection (75 mg/kg) as a positive control. We herein have summarized the mortality, body weight change, and neoplastic and nonneoplastic lesions detected in these positive control groups as representative historical positive control data. Also, we performed an interlaboratory comparison of the response of rasH2-Tg mice to MNU based on the data of 11 positive control groups from these studies. Although the body weight of rasH2-Tg mice showed lower values than that of non-Tgmice during the experimental period, body weight gain in the rasH2-Tg mice was similar to that in non-Tg mice. The mortality of rasH2-Tg mice during the study period was very low, the same as for the non-Tg mice. Incidences of spontaneous alveolar/bronchiolar adenomas and splenic hemangiomas/hemangiosarcomas were also low in the rasH2-Tg mice. Nonneoplastic lesions detected in the rasH2-Tg mice were similar to those in non-Tg mice, excluding the incidence of myopathy. There were interlaboratory differences in mortality and incidence of some lesions in the MNU-treated groups. However, the causes of death were common among the 11 laboratories and almost all the MNU-treated rasH2-Tg mice developed forestomach squamous cell papillomas/carcinomas or malignant lymphomas. This suggests that there is no appreciable difference in the response of the rasH2-Tg mouse to MNU used as a positive control. Therefore, it is concluded that MNU would be an adequate positive control compound in this testing system.
In order to evaluate a short-term carcinogenicity testing system using CB6F1 -Tg rasH2 (rasH2-Tg) mice carrying a human prototype c-Ha-ras gene, 26-week studies were conducted in 12 different facilities as a part of an International Life Science Institute Health and Environmental Science Institute (ILSI HESI) international collaborative project. In each study N-methyl-N-nitrosourea (MNU) was administered to a separate group of rasH2-Tg mice by single intraperitoneal injection (75 mg/kg) as a positive control. We herein have summarized the mortality, body weight change, and neoplastic and nonneoplastic lesions detected in these positive control groups as representative historical positive control data. Also, we performed an interlaboratory comparison of the response of rasH2-Tg mice to MNU based on the data of 11 positive control groups from these studies. Although the body weight of rasH2-Tg mice showed lower values than that of non-Tgmice during the experimental period, body weight gain in the rasH2-Tg mice was similar to that in non-Tg mice. The mortality of rasH2-Tg mice during the study period was very low, the same as for the non-Tg mice. Incidences of spontaneous alveolar/bronchiolar adenomas and splenic hemangiomas/hemangiosarcomas were also low in the rasH2-Tg mice. Nonneoplastic lesions detected in the rasH2-Tg mice were similar to those in non-Tg mice, excluding the incidence of myopathy. There were interlaboratory differences in mortality and incidence of some lesions in the MNU-treated groups. However, the causes of death were common among the 11 laboratories and almost all the MNU-treated rasH2-Tg mice developed forestomach squamous cell papillomas/carcinomas or malignant lymphomas. This suggests that there is no appreciable difference in the response of the rasH2-Tg mouse to MNU used as a positive control. Therefore, it is concluded that MNU would be an adequate positive control compound in this testing system.
Abstract. Mineralization of various degrees was found in the brains of 79 (59%) of 134 cynomolgus monkeys (Macaca fascicularis). There was no age dependency in the incidence or severity, nor were there any abnormalities in growth, weight gain, or neurologic signs, although a slight sex difference was observed. The lesions, which were basophilic and intensely positive for periodic acid-Schiff or von Kossa stain, occurred in the vascular walls of the globus pallidus in two types: globoid bodies with prominent concentric lamellar structures in and around the arteriolar and venular wall (type A) and fine granules in the media of small or medium-sized arteries (type B). Electron microscopic examination revealed dense deposits in the degenerated media of small or mediumsized arteries or the thickened walls of the arterioles. X-ray microanalysis demonstrated the presence of calcium, phosphorus, iron, zinc, magnesium, and aluminum.Key words: Cynomolgus monkeys; globus pallidus; Macaca fascicularis; vascular mineralization.In the elderly human, a mild degree of mineralization without any clinical signs is common in and around the vessel wall of the globus pallidus.2.'0-16.2' This type of severe pallidal mineralization has been observed in various disease c~nditions.~.~.~J~.~~J~.~' Vascular mineralization has also been described in the thalamus of aged mice, with the prevalence and severity reported to be dependent on mouse strains and aging.8s22.24 In monkeys, there have been few reports on the occurrence of cerebral mineralization nor have detailed morphological or histochemical studies been reported. The pathogenesis is not clear in any animal species. In routine necropsies on monkeys, we found varying degrees of mineralization in the globus pallidus of cynomolgus monkeys (Macaca fascicularis). The present paper compares light and electron microscopic findings in the monkeys with those observed in humans and mice. Materials and MethodsSixty-one male and 73 female cynomolgus monkeys that were born in the laboratory or imported from the Philippines were necropsied at 3-1 8 years of age. Monkeys were housed individually or in male/female pairs in stainless steel cages in a relatively isolated room maintained at a temperature of approximately 25 C. They were maintained according to specified guidelines6 and given a commercial primate diet (Purina Monkey Chow, Ralston Purina Co., St. Louis, MO), apples, bananas, and oranges. Water was freely provided with an automatic watering system. Samples of brains and other organs were taken from the euthanatized monkeys. After formalin fixation, the brain was sliced coronally into 5-mm-thick sections, and some sections were subjected to soft X-ray micrography. Tissues were fixed in 10% buffered formalin, and paraffin sections were made. Sections were prepared from various levels of the cerebral cortex, Ammon's horn, caudate nucleus, globus pallidus, thalamus, pons, and medulla oblongata and were stained with hematoxylin and eosin (HE), periodic acid-Schiff(PAS), alcian blue, von Kossa...
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