Background: Telomerase consists of two essential subunits, the template RNA (TR; telomerase RNA) and the catalytic subunit TERT (telomerase reverse transcriptase). Knockout mice with a mTR (mouse TR) deletion have been described and well characterized. However, mice with a mTERT (mouse TERT) deletion have not been reported.

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Abstract:A variety of neoplastic and non-neoplastic lesions in F344/DuCrj rats, which were used as control animals in chronic toxicity and carcinogenicity studies conducted at the Biosafety Research Center, Foods, Drugs and Pesticides over a 9 year period, are described. The causes of death of animals which were found dead or that were killed in a moribund condition, as well as age-associated differences in the incidence rate of various lesions at 31, 57, 83, and 109 weeks, were also analyzed. The average number of naturally-occurring tumors per rat was 1.68 in male and 0.92 in female rats. The incidence rate of malignant tumors in all animals was 12.5% in male and 11.4% in female rats. The most common tumors were leukemia and benign tumors of the endocrine and reproductive organs. As for the non neoplastic lesions, chronic nephropathy occurred more frequently in male than in female rats. Other lesions commonly observed were atrophic changes in the thymus and reproductive organs, deposits of hemosiderin or ceroid-like materials in a variety of organs, proliferative or hyperplastic changes of the bile ducts, endocrine and reproductive organs, microgranuloma, angiectasis and dilated or cystic changes in a variety of organs, fatty change in the liver and adrenals, and hepatodiaphragmatic nodules of the liver. Nearly all of the above findings increased in both incidence and severity with age. (J Toxicol Pathol 4: 1.24, 1991)

Abstract:The final version of the international harmonized nomenclature for proliferative lesions in rats was issued on June 21, 2000. The recommended nomenclature for proliferative lesions in the liver includes focus of cellular alteration, regenerative hepatocellular hyperplasia, cholangiofibrosis, cholangiofibroma, oval cell hyperplasia, hepatocellular adenoma, hepatocellular carcinoma, bile duct hyperplasia, cholangioma, cholangiocarcinoma, hepatocholangiocellular adenoma, and hepatocholangiocellular carcinoma. Foci of cellular alteration are further classified into the following phenotypes: amphophilic, diffusely basophilic, tigroid basophilic, clear cell, eosinophilic, and mixed (basophilic/eosinophilic). Hepatocellular carcinomas are divided into 3 types based on their growth patterns: acinar, solid, and trabecular. In consideration of this international harmonized nomenclature, the current classification, terminology, and diagnostic criteria for prolifrative lesions in the liver of rats recommended by the Japanese Society of Toxicologic Pathology (JSTP) were reviewed by a Working Group of the JSTP. The hepatic proliferative lesions reviewed by the present Working Group included lesions of hepatocellular, cholangiocellular, mixed hepatocholangiocellular, sinusoidal, and hemangioendothelial origins. Any comments and questions on these lesions were discussed among pathologists in the Working Group and the results of discussions were presented at the 1st seminar on the continuing education program

The Working Group for the Proliferative Lesions of the Kidney in Rats and [175][176][177][178][179][180][181][182][183][184][185][186][187][188][189][190]

Abstract:In order to standardize test procedures for evaluation of neurotoxicity of chemical exposure, a collaborative study with a common protocol based on the Organization for Economic Cooperation and Development (OECD) test guideline TG407 was conducted by eleven laboratories, using acrylamide and 3,3'-iminodipropionitrile (IDPN) as positive neurotoxicants. This report summarizes the results of this neuropathological evaluation of neurotoxicity, when acrylamide (3, 10, and 30 mg/kg) and IDPN (20, 50, and 100 mg/kg) were orally administered to rats for 28 days. The study revealed typical alterations, including degeneration of peripheral nerve fibers and Purkinje's cell necrosis with acrylamide, and axonal swelling in the brainstem and spinal cord with IDPN. In addition to the neurotoxicity, IDPN exerted toxic effects on the cerebral arteries, hyalinization of vessel walls being observed. In general, the neuropathological findings well demonstrated the neurotoxicity of both chemicals. These results indicate that neuropathological evaluation can play a crucial role in screening for potential neurotoxicants with risk for human health, the expected neurotoxic effects being detected in this collaborative study consistently in all the laboratories. (J Toxicol Pathol 2001; 14: 279-287)

ABSTRACT. The histological characteristics of 9 cases of granular cell tumors (GCTs) observed in B6C3F 1 mice were examined to determine their cellular origin. Seven of the 9 cases were found in the uterus and other 2 cases were in the subcutaneous tissue. Tumor cells had abundant granules in the cytoplasm which were stained with PAS and were resistant to diastase treatment. Ultrastructurally, the granules were identified as lysosomes. The cell surface had cytoplasmic processus showing interdigitation with adjacent cells. A character feature of the tumor cells was the presence of a desmosome-like structure on their cell surface but no basal lamina was demonstrated. Although GCTs have been considered to be derived from Schwann cells on the basis of their ultrastructural features and S-100 proteinimmunopositive findings, the absence of basal lamina in the present cases may raise a controversy as to their origin. KEY WORDS: B6C3F 1 mouse, granular cell tumor.

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