Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine.

In this Perspective article, Brian Grone and Scott Baraban examine some of the numerous nonhuman animal models of epilepsy. The authors outline how traditional animal models have advanced our understanding of seizure initiation and epileptogenesis and also describe how the use of more 'non-traditional' model systems may further improve insight into both disease mechanisms as well as potential therapeutic avenues. Human epilepsies encompass a wide variety of clinical, behavioral and electrical manifestations. Correspondingly, studies of this disease in nonhuman animals have brought forward an equally wide array of animal models; that is, species and acute or chronic seizure induction protocols. Epilepsy research has a long history of comparative anatomical and physiological studies on a range of mostly mammalian species. Nonetheless, a relatively limited number of rodent models have emerged as the primary choices for most investigations. In many cases, these animal models are selected on the basis of convenience or tradition, although technical or experimental rationale does, and should, factor into these decisions. More complex mammalian brains and genetic model organisms including zebrafish have been studied less, but offer substantial advantages that are becoming widely recognized.

/pdf/animal-models-in-epilepsy-research-legacies-and-new-3ndczy55u3.pdf

Animal models in epilepsy research: legacies and new directions.

The renaissance of the laboratory rabbit as a reproductive model for human health is closely related to the growing evidence of periconceptional metabolic programming and its determining effects on offspring and adult health. Advantages of rabbit reproduction are the exact timing of fertilization and pregnancy stages, high cell numbers and yield in blastocysts, relatively late implantation at a time when gastrulation is already proceeding, detailed morphologic and molecular knowledge on gastrulation stages, and a hemochorial placenta structured similarly to the human placenta. To understand, for example, the mechanisms of periconceptional programming and its effects on metabolic health in adulthood, these advantages help to elucidate even subtle changes in metabolism and development during the pre- and peri-implantation period and during gastrulation in individual embryos. Gastrulation represents a central turning point in ontogenesis in which a limited number of cells program the development of the three germ layers and, hence, the embryo proper. Newly developed transgenic and molecular tools offer promising chances for further scientific progress to be attained with this reproductive model species.

https://rep.bioscientifica.com/downloadpdf/journals/rep/144/1/1.pdf

Rabbit as a reproductive model for human health

Staphylococcus aureus is a highly successful bacterial pathogen owing to its abundance of cell surface and secreted virulence factors. It is estimated that 30% of the population is colonized with S. aureus, usually on mucosal surfaces, and methicillin-resistant S. aureus is a major public health concern. There have been multiple attempts to develop an S. aureus vaccine using one or more cell surface virulence factors as antigens; all of these vaccine trials have failed. In this Opinion article, we suggest that an over-reliance on rodent models and a focus on targeting cell surface components have been major contributing factors to this failure.

/pdf/models-matter-the-search-for-an-effective-staphylococcus-4hehukj3pv.pdf

Models matter: the search for an effective Staphylococcus aureus vaccine

Human epilepsies encompass a wide variety of clinical, behavioral and electrical manifestations. Correspondingly, studies of this disease in nonhuman animals have brought forward an equally wide array of animal models, i.e. species and acute or chronic seizure induction protocols. Epilepsy research has a long history of comparative anatomical and physiological studies on a range of mostly mammalian species. Nonetheless, a relatively limited number of rodent models emerged as the primary choices for most epilepsy-related investigations. In many cases these animal models are selected based on convenience or tradition, though technical or experimental rationale does, and should, factor into these decisions. More complex mammalian brains and, especially, genetic model organisms including zebrafish have been studied less but offer significant advantages that are being widely recognized.

https://biorxiv.org/content/biorxiv/early/2015/01/03/013136.full.pdf

Animal models in epilepsy research: legacies and new directions

The laboratory rabbit (Oryctolagus cuniculus) is widely used as a model for human diseases, because of its size, which permits non-lethal monitoring of physiological changes and similar disease characteristics. Novel transgenic tools such as, the zinc finger nuclease method and the sleeping beauty transposon mediated or BAC transgenesis were recently adapted to the laboratory rabbit and opened new opportunities in precise tissue and developmental stage specific gene expression/silencing, coupled with increased transgenic efficiencies. Many facets of human development and diseases cannot be investigated in rodents. This is especially true for early prenatal development, its long-lasting effects on health and complex disorders, and some economically important diseases such as atherosclerosis or cardiovascular diseases. The first transgenic rabbits models of arrhythmogenesis mimic human cardiac diseases much better than transgenic mice and hereby underline the importance of non-mouse models. Another emerging field is epigenetic reprogramming and pathogenic mechanisms in diabetic pregnancy, where rabbit models are indispensable. Beyond that rabbit is used for decades as major source of polyclonal antibodies and recently in monoclonal antibody production. Alteration of its genome to increase the efficiency and value of the antibodies by humanization of the immunoglobulin genes, or by increasing the expression of a special receptor (Fc receptor) that augments humoral immune response is a current demand.

On the emerging role of rabbit as human disease model and the instrumental role of novel transgenic tools

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On the emerging role of rabbit as human disease model and the instrumental role of novel transgenic tools