Therefore, animal models appear more useful as models of specific disease targets and pathways than of the complete human disease. To optimize their use in that manner, our advisory panel recommended choosing models for preclinical studies that exhibit significant selleck chemicals llc and well-characterized pathology relevant to the disease process of interest (that is, amyloid plaques, tau pathology, neuronal loss, oxidative stress/inflammatory changes, and so on). In addition, models that do not rely solely on mutated human genes to induce pathology are currently underused and can be quite informative. These include aged rodents, pharmacologically and surgically induced models, and other non-transgenic models (Table ?(Table1).1). Since there is no one model for AD, hypothesis testing in multiple models is preferable in order to provide better preclinical validation.

In the following sections, we present the panel’s recommendations and guidelines for the design, execution, and interpretation of preclinical studies. The objective of this panel was to improve the predictive value of animal models for clinical benefit. Know your model Many transgenic lines show high variability in the extent and time course of expression of disease phenotypes. Table ?Table22 illustrates common factors affecting phenotype variability, including environmental factors, age, sex, genetic background, litter, transgene copy number, and health status. Not all of these variables can be avoided, but measures can be taken so that phenotype changes due to such factors can be properly noted and potentially corrected [7-9].

Table 2 Major factors affecting phenotypic variability in mice Important points to keep in mind ? Maintain good communication among laboratory members to track deviations from expected phenotypes. Keep careful records to track whether a change in phenotype occurs. ? Identify issues with breeding, such as longer litter intervals, smaller litter sizes, and fewer pregnancies. Identifying such problems early will help keep production on track. ? Screen gene copy numbers and transgene expression level regularly. Document and report. ? Freeze embryos early during characterization of the transgenic line in case phenotypic drift necessitates rederivation of colony. ? Consider your genetic background: Mice may be healthier and more viable on a hybrid background, but genetic drift must be controlled to avoid confounding variables.

Keep in mind that certain inbred strains are more prone to characteristics like blindness, Drug_discovery hearing loss, selleckchem and aggression. ? If working with an outside breeder or contract research organization, ask to see historical data on the colony. These data should include rearing conditions such as light cycle, housing type, diet, and health status as well as breeding schemes to assess genetic management of the strain background(s) in the colony.