Proliferative and Nonproliferative Lesions of the Rat and Mouse Central and Peripheral Nervous Systems

Kaufmann, Wolfgang; Bolon, Brad; Bradley, Alys; Butt, Mark T.; Czasch, Stephanie; Garman, Robert H.; George, Christian; Gröters, Sibylle; Krinke, G.; Little, P B; McKay, Jenny; Narama, Isao; Rao, Deepa B.; Shibutani, Makoto; Sills, Robert C.

doi:10.1177/0192623312439125

Cited by 118 publications

(149 citation statements)

References 227 publications

(783 reference statements)

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“…Judging from the histological nature and the mode of incidences, the other histologic changes than the above-mentioned ones were considered not to be specific for NOG mice (Kaufmann et al, 2012;Pearse, 2006b;Khosla and Ovalle, 1986;Hardisty andBoorma., 1999: Leininger et al, 1999;Creasy et al, 2012;Dixon et al, 2014;Long and Leininger, 1999).…”

Section: Discussionmentioning

confidence: 99%

Background data on NOD/Shi-scid IL-2Rγnull mice (NOG mice)

et al. 2017

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-To obtain background data of NOD/Shi-scid IL-2Rγ null (NOG) mice, severely immunedeficient mice, a total of 120 animals were examined at 7, 26 and 52 weeks-old (20 mice/sex/group). The survival rate at 52 weeks-old was 95% (19/20) in both sexes. Clinically, circling behavior in one direction along the cage wall was observed in males after 8 weeks and females after 47 weeks-old, and hunchback position was found in males after 32 weeks-old. Hematologically, lymphocyte count markedly decreased at all ages, while white blood cell count increased in several mice at 52 weeks-old. Blood chemistry results revealed high values of aspartate aminotransferase, lactate dehydrogenase and creatine phosphokinase in some females at 26 weeks-old, without any related histological change. Histologically, lymphoid hypoplasia characterized by severe lymphocyte depletion with poorly developed tissue architectures was observed. In addition, spongiotic change in the nerve tissue was observed in both sexes at 7 and 26 weeks-old, and intracytoplasmic materials known as tubular aggregates in the skeletal muscles were found in males terminated at 26 and 52 weeks-old and in females at 52 weeks-old. Malignant lymphoma was found in one female euthanized at 20 weeks-old. Further, small intestinal adenoma, hepatocellular adenoma, leukemia, cerebral lipomatous hamartoma, Harderian gland adenoma and uterine polyp were also observed, and their incidences were low except for that of uterine polyp. This study provided detailed background data on NOG mice up to 52 weeks-old and provided information on appropriate use of NOG mice in the various research fields.

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Section: Discussionmentioning

confidence: 99%

Background data on NOD/Shi-scid IL-2Rγnull mice (NOG mice)

et al. 2017

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“…Generally accepted terms were used in the diagnosis of proliferative and nonproliferative lesions (STP/ARP/AFIP SSNDC Guides for Toxicologic Pathology). Classification and nomenclature used in this project are those being considered in the recently published International Harmonization of Nomenclature and Diagnostic Criteria for lesions in rats and mice (Kaufmann et al 2012). All neoplastic findings in each study underwent pathology peer review, and all data were reviewed by the Quality Assurance Department at Charles River's Edinburgh facility prior to the release of the final pathology report.…”

Section: Pathological Evaluationmentioning

confidence: 99%

Incidence of Spontaneous Central Nervous System Tumors in CD-1 Mice and Sprague-Dawley, Han-Wistar, and Wistar Rats Used in Carcinogenicity Studies

2014

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The incidence and range of spontaneous central nervous system tumors were determined in control Charles River rodents (Sprague-Dawley, HanWistar, Wistar rats, and CD-1 mice) from regulatory carcinogenicity studies carried out over the period 2002 to 2013 and were compared with the previously published data. In both species, the brain was notably more affected than the spinal cord. Incidences were comparable overall between rat strains (2.33%, 2.54%, and 2.89% in Wistar, Sprague-Dawley, and Han-Wistar strains, respectively) and were low in CD-1 mice (0.42% in 104-week studies and 0.2% in 80-week studies). Predominant tumor types were granular cell tumors in Wistar and Han-Wistar rats and malignant astrocytoma in Sprague-Dawley rats. Male rats were more frequently affected than females, but no sex predilection was apparent in CD-1 mice. Occasional earlyonset tumors were diagnosed in rats from study week 23 onward. It is hoped that these results will provide the pathologist and the toxicologist with an up-to-date database of background neoplastic findings in widely used rodent strains.

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“…Some nerve cells remained within the lesion. All mixed tumors corresponded to low-grade malignant mixed tumor, according to INHAND (Kaufmann et al 2012). (Figure 7).…”

Section: Histological Characteristics Of the Tumorsmentioning

confidence: 99%

GFAP-Positive Neoplastic Astrocytes in Spontaneous Oligodendrogliomas and Mixed Gliomas of Rats

et al. 2012

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It is generally said that neoplastic cells are immunohistochemically negative for glial fibrillary acidic protein (GFAP) in rat spontaneous astrocytomas, and there are no reports describing the existence of GFAP-positive neoplastic astrocytes in rat spontaneous oligodendrogliomas and mixed gliomas which contain neoplastic astrocytes. In the present study, to clarify whether GFAP-positive neoplastic astrocytes exist in rat spontaneous oligodendrogliomas and mixed gliomas or not, immunohistochemical examination was performed on spontaneous oligodendrogliomas (26 cases) and mixed gliomas (5 cases) collected from the carcinogenicity studies and short-term toxicity studies. The neoplastic cells that constitute oligodendrogliomas and mixed gliomas were morphologically classified into five types: round A, round B, round C, spindle, and bizarre. The cells of round A, B, and C types were thought to be neoplastic oligodendrocytes because of their positive immunostainability for Olig2. The origin of bizarre cells was obscure because they were negative for Olig2, GFAP, and nestin. The spindle cells were considered to be neoplastic astrocytes, because some of them were positive for GFAP or nestin, and GFAP-positive spindle cells could be morphologically distinguished from reactive astrocytes. In conclusion, the present study clarified for the first time that GFAP-positive neoplastic astrocytes exist in rat spontaneous gliomas.

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Proliferative and Nonproliferative Lesions of the Rat and Mouse Central and Peripheral Nervous Systems

Cited by 118 publications

References 227 publications

Background data on NOD/Shi-<i>scid</i> IL-2Rγ<sup>null</sup> mice (NOG mice)

Background data on NOD/Shi-<i>scid</i> IL-2Rγ<sup>null</sup> mice (NOG mice)

Incidence of Spontaneous Central Nervous System Tumors in CD-1 Mice and Sprague-Dawley, Han-Wistar, and Wistar Rats Used in Carcinogenicity Studies

GFAP-Positive Neoplastic Astrocytes in Spontaneous Oligodendrogliomas and Mixed Gliomas of Rats

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