Animal models for metabolic, neuromuscular and ophthalmological rare diseases

Abstract

Animal models are important tools in the discovery and development of treatments for rare diseases, particularly given the small populations of patients in which to evaluate therapeutic candidates. Here, we provide a compilation of mammalian animal models for metabolic, neuromuscular and ophthalmological orphan-designated conditions based on information gathered by the European Medicines Agency's Committee for Orphan Medicinal Products (COMP) since its establishment in 2000, as well as from a review of the literature. We discuss the predictive value of the models and their advantages and limitations with the aim of highlighting those that are appropriate for the preclinical evaluation of novel therapies, thereby facilitating further drug development for rare diseases.

Integrative Systems Biology Investigation of Fabry Disease

“…The FD mouse model presents a normal adult lifespan with normal blood and urine analysis, but has a number of limitations compared to the human disease including fewer symptoms with no evident histological lesions in stained sections of the kidneys, liver, heart, spleen, lungs and brain compared to humans, even though this animal model mimics the main neurological features of FD, including reduced locomotor activity, impairment of balance and coordination and diminished sensitivity to painful stimuli. On the other hand, the animal model shows progressive and demarcated accumulation of Gb3 in the kidneys and liver which makes the mouse model suitable for the development of enzyme replacement therapies via the assessment of the clearance of accumulated Gb3 in the affected organs [13]. …”

Catheterization of the gallbladder: A novel mouse model of severe acute cholangitis

“…To study this disease, the animal model of SAC has been established in rodents, such as rats[8,18,19]. As the most commonly used experimental animal[20], the anatomical construction of bile ducts in mice is more similar to that in humans because rats do not have a gallbladder. The gallbladder slows down the tremendous increase in biliary pressure at the beginning of biliary obstruction.…”

Animal Models with a Genetic Alteration of the ACE2/Ang-(1-7)/Mas Axis

“…In biomedical research, the use of rats and mice has become a major tool, considering the easiness of breeding, growth, and maintenance and the similarity with human organisms in most cardiovascular and metabolic systems. 3 Currently, the use of transgenic technologies to access animal physiology is routine, but the pioneering work was performed in the 1980s. The first successful genetic modifications of a mouse were achieved by Gordon and colleagues.…”

“…80 Furthermore, chronic elevation of circulating Ang-(1-7) levels considerably improved the lipid and glycolytic profile and lowered the fat mass accompanied by a decrease in triglycerides and cholesterol in plasma and an improved glucose tolerance and insulin sensitivity and reduced gluconeogenesis in the liver. 55,56 Transgenic Mice and Rats Overexpressing Ang- (1)(2)(3)(4)(5)(6)(7) in the Heart Transgenic mice carrying the Ang-(1-7)-releasing construct under the control of the alpha-cardiac myosin heavy-chain promoter exhibit about an eightfold increase of the peptide in the heart and show a normal basic cardiac function but are protected from hypertensive cardiac hypertrophy induced by Ang II infusion 58 but not from myocardial infarction. 81 Transgenic rats generated with the same construct showed a slightly improved resting cardiac function and were also protected from hypertrophy in this case induced by isoproterenol.…”