Poor reproducibility of published research employing model organisms and lack of transparency of study designs are areas of concern for the scientific community. These issues can profoundly affect the interpretation of preclinical studies and must be addressed as genome editing technologies permit rapid modeling of disease-associated genetic variation and translation to the clinic. At the heart of reproducibility issues are the model organism themselves. Stability and identity of the genetic background, genome integrity, and specifics of genetically engineered alleles often vary between studies. Moreover, variabilities in the quality of study designs used by different groups, including differences in the environment, methods for phenotyping, instrumentation, sample sizes, and data analysis and statistical methods, can significantly impact study conclusions. Centralization and standardization of production, maintenance, and phenotyping pipelines for precision and pre-clinical animal models can begin to address issues with study reproducibility and transparency.