Comparison of the Class Effects of Antisense Oligonucleotides in CByB6F1-Tg(HRAS)2Jic and CD-1 Mice
| Autor: | Laura S. Zwick, Jill Hsiao, Chris Papagiannis, Jeffery A. Engelhardt, Noah Post, Scott P. Henry, Tae-Won Kim, John Matson, Sebastien A. Burel, Christine Hoffmaster |
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| Rok vydání: | 2018 |
| Předmět: |
Male
medicine.medical_specialty Chemokine Time Factors 040301 veterinary sciences medicine.medical_treatment Mice Transgenic Pharmacology Toxicology 030226 pharmacology & pharmacy Pathology and Forensic Medicine 0403 veterinary science 03 medical and health sciences 0302 clinical medicine Species Specificity Internal medicine Toxicity Tests medicine Animals Tissue Distribution HRAS Molecular Biology Carcinogen Hemizygote Mice Inbred ICR Oligoribonucleotides Hematology Base Sequence biology Oligonucleotide Wild type Organ Size 04 agricultural and veterinary sciences Cell Biology Oligonucleotides Antisense Genes ras Cytokine Organ Specificity Carcinogens biology.protein Cytokines Female Histopathology |
| Zdroj: | Toxicologic Pathology. 47:82-92 |
| ISSN: | 1533-1601 0192-6233 |
| Popis: | The 6-month Tg.rasH2 mouse carcinogenicity model provides an acceptable alternative to the 2-year carcinogenicity study in CD-1 mice. However, key questions related to the use of this model for testing antisense oligonucleotides (ASOs) include the similarity in the biologic response between mouse strains and the feasibility of using data from the CD-1 mouse to set doses and dose schedules for a Tg.rasH2 carcinogenicity study. To evaluate the potential strain differences, four distinct 2′- O-(2-methoxyethyl) ASOs were administered to CByB6F1 (wild type), Tg.rasH2 (hemizygous), and CD-1 mice. There were no meaningful differences in clinical signs, body weight, food consumption, or serum chemistry and hematology parameters. Histopathology evaluation indicated little to no difference in the spectrum or magnitude of changes present. The cytokine/chemokine response was also not appreciably different between the strains. This was consistent with the similarity in ASO concentration in the liver between the mouse strains tested. As the class effects of the ASOs were not meaningfully different between CD-1, CByB6F1, or Tg.rasH2 mice, data from nonclinical studies in CD-1 mice can be used for dose selection and expectation of effect in the Tg.rasH2 mouse. |
| Databáze: | OpenAIRE |
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