Quality INSIGHTS

On May 25, 2017, Dr. Madhav Paranjpe presented a webinar on the state of evidence surrounding the use of Tg.RasH2 carcinogenicity studies as a substitute for the two-year mouse bioassay. His presentation — "Historical Control Database of Spontaneous Lesions (Neoplastic & Non-Neoplastic) in Transgenic Tg.rasH2 Mice" — covered evidence drawn from fifty peer-reviewed studies, personal experience, and analysis of the growing body of historical control data supporting...

While evidence mounts in support of revised carcinogenicity testing guidelines, the number of Carcinogenicity Assessment Documents (CAD) submitted to the ICH S-1 expert working group fell below expected levels. After extending the submission period by two years9, the expert working group (EWG) will meet in June of 2017 to review the conclusions of drug regulatory agencies on the viability of excluding some pharmaceutical agents from the requirement...

Researchers from the University of Iowa inadvertently identified an Nlrp12 missense mutation which inhibits immune responses in C57BL/6J mice. Further investigation reveals the mutation occurred prior to 1971, potentially impacting decades of research conducted on affected mouse models. Reduced Neutrophil Recruitment in C57BL/6J In this study, the authors compared C57BL/6J and C57BL/6NTac mice and noted that C57BL/6J mice had reduced neutrophil recruitment. Initially hypothesizing the difference was...

Recently, a novel rodent polyomavirus, rat polyomavirus 2 (RPyV2), was discovered. This new agent was isolated from a colony of highly immunodeficient rats which developed clinical illness, including emaciation, labored breathing and mortality, particularly among breeding females and pups. IDEXX BioResearch, working collaboratively with the affected academic institution, was finally able to identify the cause as a novel rat virus, which they named Rattus norvegicus polyomavirus 2...

The Sprague Dawley® (SD) rat is one of the most popular outbred stocks, with application across many therapeutic areas as well as ADMET studies. The SD is an outbred stock, meaning that there is genetic variation within the stock, and each individual varies in genetic makeup. Genetic variation is maintained through well-defined rotational mating schemes, which are designed to maintain heterozygosity within the population over time. The...

What are the most important factors in assessing the quality of an animal model? In Part I, we discussed two of the four quality considerations for using laboratory mice: health and genetics. To recap: It's important to understand the different health standards when assessing an animal model. Commercial providers often make them available online, or they can be requested from the sending facility. With genetics, using polymerase...

Which elements of quality should you consider when conducting a study with animal models? Let's start with the definition of quality from Merriam-Webster: Quality [qual-i-ty] noun How good or bad something is. A characteristic or feature that someone or something has, something that can be noticed as a part of a person or thing. A high level of value or excellence. There are four elements which affect...

Researchers unfamiliar with mouse genetics can be confused by complex strain nomenclature, leaving them unsure how to select controls for a particular test strain. The nomenclature of congenic mice records a wealth of useful information, including both donor and recipient strains and mutations of interest. One common example of this is confusion around background strain for GEM and mutant lines. While it is common now to make...

Taconic produces rodent models at several different health standards. How do you know which health designation to choose when ordering animals? Taconic rodent models are available at multiple health standards, enabling researchers to choose the most appropriate model for their studies. These five health standards are defined by the progressive exclusion of foreign organisms. The general health standard for most immunocompetent models is Murine Pathogen Free™ (MPF™)....

75% of mouse carcinogenicity studies submitted to the FDA utilize the rasH2 mouse model (Tg.rasH2), a model accepted by the FDA as an alternative to the two-year in vivo bioassay for predicting human carcinogenic risk. In an evolving carcinogenicity testing landscape, with the utility of two-year rat bioassay under re-consideration and changes under consideration to the ICH guidelines for carcinogenic risk assessment, several key questions come to...