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Renal Tumors in 26-Week Tg.Rash2 Mice Carcinogenicity Studies
Madhav G Paranjpe1, Jessica L Belich2, Marie E McKeon2
1BioReliance by SAFC, Rockville, Maryland, USA madhav.paranjpe@bioreliance.com.
Abstract:
We report renal tubular adenomas and a carcinoma in 26-week Tg.rasH2 mouse carcinogenicity studies, which have not been reported to date either at our facility or in other published data. However, during the year 2014, renal tubular tumors were present in 4 studies conducted at our facility. Because of their morphological similarity to the amphophilic-vacuolar (AV) phenotypic variant of renal tubule tumors noted in Sprague-Dawley and Fischer 344 rats, which are thought to be familial, as well as the genetic homogeneity of Tg.rasH2 mice, we tracked the parents of these mice with tumors in each study. The origin of these tumors could not be traced back to any of the parents or even an animal barrier, and these tumors were not attributed to the vehicle or test article. Although the exact mechanism of tumorigenesis was not known, based on the available information, the development of renal tumors in these mice was considered random and spontaneous.
Insights
Spontaneous renal tubular adenomas and carcinoma were observed in Tg.rasH2 mice during carcinogenicity studies. These novel findings in mouse models suggest random tumor development unrelated to study compounds.
Area of Science:
- Toxicology
- Oncology
- Genetics
Background:
- Renal tubular tumors, specifically adenomas and carcinomas, are uncommon findings in Tg.rasH2 mouse carcinogenicity studies.
- Previous reports from our facility and published literature have not documented these specific renal tumors in this mouse model.
Purpose of the Study:
- To investigate the occurrence and potential origins of newly observed renal tubular adenomas and carcinomas in Tg.rasH2 mice.
- To determine if the renal tumors were linked to genetic factors, environmental contaminants, or study-related treatments.
Main Methods:
- Tg.rasH2 mice from carcinogenicity studies conducted in 2014 were examined for renal tumors.
- Parental lineage and animal handling procedures were reviewed to trace the origin of the tumors.
- Morphological similarities to known rat renal tumor variants were assessed.
Main Results:
- Renal tubular adenomas and a carcinoma were identified in 26-week-old Tg.rasH2 mice.
- Tumor development was not linked to parental lineage, animal facility barriers, vehicle, or test articles.
- The observed renal tumors exhibited morphological similarities to the amphophilic-vacuolar (AV) phenotypic variant found in rats.
Conclusions:
- The development of renal tumors in Tg.rasH2 mice appears to be a spontaneous and random event.
- Further investigation into the precise mechanism of tumorigenesis is warranted.
- These findings highlight the importance of characterizing spontaneous lesions in genetically modified mouse models for carcinogenicity studies.
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