12. Background
Scientific background information for an animal study should demonstrate a clear evidence gap and explain why an in vivo approach was warranted. Systematic reviews of the animal literature provide the most convincing evidence that a research question has not been conclusively addressed, by showing the extent of current evidence within a field of research. They can also inform the choice of animal model by providing a comprehensive overview of the models used along with their benefits and limitations [1-3].
Describe the rationale and context of the study and how it relates to other research, including relevant references to previous work. Outline evidence underpinning the hypothesis or objectives and explain why the experimental approach is best suited to answer the research question.
References
- Avey MT, Fenwick N and Griffin G (2015). The use of systematic reviews and reporting guidelines to advance the implementation of the 3Rs. Journal of the American Association for Laboratory Animal Science : JAALAS. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382619/
- Hooijmans CR and Ritskes-Hoitinga M (2013). Progress in using systematic reviews of animal studies to improve translational research. PLOS Medicine. doi: 10.1371/journal.pmed.1001482
- Sena ES, Currie GL, McCann SK, Macleod MR and Howells DW (2014). Systematic reviews and meta-analysis of preclinical studies: why perform them and how to appraise them critically. J. Cereb. Blood Flow Metab. doi: 10.1038/jcbfm.2014.28
Example 1
“For decades, cardiovascular disease has remained the leading cause of mortality worldwide...[and] cardiovascular research has been performed using healthy and young, non-diseased animal models. Recent failures of cardioprotective therapies in obese insulin-resistant, diabetic, metabolic syndrome-affected and aged animals that were otherwise successful in healthy animal models has highlighted the need for the development of animal models of disease that are representative of human clinical conditions…In the clinical setting, elderly male patients often present with both testosterone deficiency (TD) and the metabolic syndrome (MetS). A strong and compounding association exists between MetS and TD which may have significant impact on cardiovascular disease and its outcomes which is not addressed by current models…their mutual presentation in the clinical setting warrants the development of appropriate animal models of the MetS with hypogonadism, especially in the context of cardiovascular disease research.” [1]
References
- Donner DG, Elliott GE, Beck BR, Bulmer AC and Du Toit EF (2015). Impact of Diet-Induced Obesity and Testosterone Deficiency on the Cardiovascular System: A Novel Rodent Model Representative of Males with Testosterone-Deficient Metabolic Syndrome (TDMetS). PLOS ONE. doi: 10.1371/journal.pone.0138019
Provide enough detail for the reader to assess the suitability of the animal model used to address the research question. Include information on the rationale for choosing a particular species, explain how the outcome measures assessed are relevant to the condition under study, and how the model was validated. Stating that an animal model is commonly used in the field is not appropriate, and a well-considered, detailed rationale should be provided.
When the study models an aspect of a human disease, indicate how the model is appropriate for addressing the specific objectives of the study [1]. This can include a description of how the induction of the disease, disorder, or injury is sufficiently analogous to the human condition, how the model responds to known clinically-effective treatments, how similar symptoms are to the clinical disease and how animal characteristics were selected to represent the age, sex, and health status of the clinical population [2].
References
- Willner P (1986). Validation criteria for animal models of human mental disorders: Learned helplessness as a paradigm case. Progress in Neuro-Psychopharmacology and Biological Psychiatry. doi: 10.1016/0278-5846(86)90051-5
- van der Worp HB, Howells DW, Sena ES, Porritt MJ, Rewell S, O'Collins V and Macleod MR (2010). Can Animal Models of Disease Reliably Inform Human Studies? PLOS Medicine. doi.org/10.1371/journal.pmed.1000245
Example 1
“…we selected a pilocarpine model of epilepsy that is characterized by robust, frequent spontaneous seizures acquired after a brain insult, well-described behavioral abnormalities, and poor responses to antiepileptic drugs. These animals recapitulate several key features of human temporal lobe epilepsy, the most common type of epilepsy in adults.” [1]
Example 2
“Transplantation of healthy haematopoietic stem cells (HSCs) is a critical therapy for a wide range of malignant haematological and non-malignant disorders and immune dysfunction…Zebrafish are already established as a successful model to study the haematopoietic system, with significant homology with mammals…Imaging of zebrafish transparent embryos remains a powerful tool and has been critical to confirm that the zebrafish Caudal Haematopoietic Tissue (CHT) is comparable to the mammalian foetal haematopoietic niche...Xenotransplantation in zebrafish embryos has revealed highly conserved mechanisms between zebrafish and mammals. Recently, murine bone marrow cells were successfully transplanted into zebrafish embryos, revealing highly conserved mechanism of haematopoiesis between zebrafish and mammals…Additionally, CD34 enriched human cells transplanted into zebrafish were shown to home to the CHT and respond to zebrafish stromal-cell derived factors…” [2]
References
- Hunt RF, Girskis KM, Rubenstein JL, Alvarez–Buylla A and Baraban SC (2013). GABA progenitors grafted into the adult epileptic brain control seizures and abnormal behavior. Nature neuroscience. doi:10.1038/nn.3392
- Hamilton N, Sabroe I and Renshaw SA (2018). A method for transplantation of human HSCs into zebrafish, to replace humanised murine transplantation models. F1000Res. doi:10.12688/f1000research.14507.2