scholarly journals Animal Models Are Valid to Uncover Disease Mechanisms

PLoS Genetics ◽  
2016 ◽  
Vol 12 (5) ◽  
pp. e1006013 ◽  
Author(s):  
Wolfgang Wurst
Keyword(s):  
Animal Models ◽  
Disease Mechanisms

scholarly journals Modeling Rare Human Disorders in Mice: The Finnish Disease Heritage

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3158
Author(s):  
Tomáš Zárybnický ◽  
Anne Heikkinen ◽  
Salla M. Kangas ◽  
Marika Karikoski ◽  
Guillermo Antonio Martínez-Nieto ◽  
...  
Keyword(s):  
Human Physiology ◽  
Animal Models ◽  
Mouse Models ◽  
Rare Diseases ◽  
Disease Modeling ◽  
Common Disease ◽  
Molecular Pathways ◽  
Finnish Population ◽  
Disease Mechanisms ◽  
Human Disorders

The modification of genes in animal models has evidently and comprehensively improved our knowledge on proteins and signaling pathways in human physiology and pathology. In this review, we discuss almost 40 monogenic rare diseases that are enriched in the Finnish population and defined as the Finnish disease heritage (FDH). We will highlight how gene-modified mouse models have greatly facilitated the understanding of the pathological manifestations of these diseases and how some of the diseases still lack proper models. We urge the establishment of subsequent international consortiums to cooperatively plan and carry out future human disease modeling strategies. Detailed information on disease mechanisms brings along broader understanding of the molecular pathways they act along both parallel and transverse to the proteins affected in rare diseases, therefore also aiding understanding of common disease pathologies.

scholarly journals Viral Delivery Systems for CRISPR

Viruses ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 28 ◽  
Author(s):  
Christine L. Xu ◽  
Merry Z. C. Ruan ◽  
Vinit B. Mahajan ◽  
Stephen H. Tsang
Keyword(s):  
Animal Models ◽  
Precision Medicine ◽  
Viral Vectors ◽  
Delivery Systems ◽  
Treatment Targets ◽  
Disease Mechanisms

The frontiers of precision medicine have been revolutionized by the development of Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR)/Cas9 as an editing tool. CRISPR/Cas9 has been used to develop animal models, understand disease mechanisms, and validate treatment targets. In addition, it is regarded as an effective tool for genome surgery when combined with viral delivery vectors. In this article, we will explore the various viral mechanisms for delivering CRISPR/Cas9 into tissues and cells, as well as the benefits and drawbacks of each method. We will also review the history and recent development of CRISPR and viral vectors and discuss their applications as a powerful tool in furthering our exploration of disease mechanisms and therapies.

scholarly journals Preclinical models of arthritis for studying immunotherapy and immune tolerance

2021 ◽  
pp. annrheumdis-2021-220043
Author(s):  
Gavin R Meehan ◽  
Ranjeny Thomas ◽  
Shaima Al Khabouri ◽  
Pascale Wehr ◽  
Catharien MU Hilkens ◽  
...  
Keyword(s):  
Animal Models ◽  
Term Treatment ◽  
Response To Treatment ◽  
Disease Mechanisms ◽  
Self Tolerance ◽  
Long Term Treatment ◽  
Disease Induction ◽  
Preclinical Animal Models ◽  
End Stage

Increasingly earlier identification of individuals at high risk of rheumatoid arthritis (RA) (eg, with autoantibodies and mild symptoms) improves the feasibility of preventing or curing disease. The use of antigen-specific immunotherapies to reinstate immunological self-tolerance represent a highly attractive strategy due to their potential to induce disease resolution, in contrast to existing approaches that require long-term treatment of underlying symptoms.Preclinical animal models have been used to understand disease mechanisms and to evaluate novel immunotherapeutic approaches. However, models are required to understand critical processes supporting disease development such as the breach of self-tolerance that triggers autoimmunity and the progression from asymptomatic autoimmunity to joint pain and bone loss. These models would also be useful in evaluating the response to treatment in the pre-RA period.This review proposes that focusing on immune processes contributing to initial disease induction rather than end-stage pathological consequences is essential to allow development and evaluation of novel immunotherapies for early intervention. We will describe and critique existing models in arthritis and the broader field of autoimmunity that may fulfil these criteria. We will also identify key gaps in our ability to study these processes in animal models, to highlight where further research should be targeted.

Considerations for Translational Research in the Study of Adult Cognitive Disorders

2019 ◽  
pp. 827-851
Author(s):  
Erich S. Franz ◽  
Sarah E. Chancellor ◽  
Lee E. Goldstein
Keyword(s):  
Health Care ◽  
Animal Models ◽  
Translational Research ◽  
Human Subjects ◽  
Cognitive Disorders ◽  
Health Care Outcomes ◽  
Cognitive Domains ◽  
Complex Interactions ◽  
Disease Mechanisms ◽  
Care Outcomes

Adult cognitive disorders exact a staggering burden on worldwide health care, with the need for efficacious and accessible treatments growing every day. The ability to probe questions relevant to normal or aberrant cognition in humans makes animal models indispensable tools in translational research. The use of animal models enables detailed investigation of complex interactions between genes, environment, and cognition that would be difficult or impossible in human subjects or populations. However, special consideration must be given to create specific, translatable models of human cognitive disorders. First, a model must prove statistically reliable, reproducible, and valid. Successful translational research requires thoughtful consideration and careful deployment of reliable, well-chosen animal models that are appropriately matched to their experimental purpose. In addition, to ensure specificity of a model to one disorder, it is prudent to focus on clusters of clinical features and disease-specific phenotypes in addition to environmental and genetic risk factors. Many neurological disorders share symptomatic elements in common, which drives the necessity for relevant cognitive domains to the disease in question to be carefully considered and replicated. Thoughtfully created animal models facilitate translational research aimed at understanding disease mechanisms and developing effective diagnostics, therapeutics, and preventive strategies to achieve better health care outcomes for people affected by cognitive disorders.

scholarly journals Large Animal Models of Inherited Retinal Degenerations: A Review

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 882 ◽  
Author(s):  
Paige A. Winkler ◽  
Laurence M. Occelli ◽  
Simon M. Petersen-Jones
Keyword(s):  
Animal Models ◽  
Vision Loss ◽  
Transgenic Animals ◽  
Large Animal ◽  
Retinal Degenerations ◽  
Large Animal Models ◽  
Disease Mechanisms ◽  
Laboratory Rodents ◽  
High Acuity ◽  
Retinal Region

Studies utilizing large animal models of inherited retinal degeneration (IRD) have proven important in not only the development of translational therapeutic approaches, but also in improving our understanding of disease mechanisms. The dog is the predominant species utilized because spontaneous IRD is common in the canine pet population. Cats are also a source of spontaneous IRDs. Other large animal models with spontaneous IRDs include sheep, horses and non-human primates (NHP). The pig has also proven valuable due to the ease in which transgenic animals can be generated and work is ongoing to produce engineered models of other large animal species including NHP. These large animal models offer important advantages over the widely used laboratory rodent models. The globe size and dimensions more closely parallel those of humans and, most importantly, they have a retinal region of high cone density and denser photoreceptor packing for high acuity vision. Laboratory rodents lack such a retinal region and, as macular disease is a critical cause for vision loss in humans, having a comparable retinal region in model species is particularly important. This review will discuss several large animal models which have been used to study disease mechanisms relevant for the equivalent human IRD.

The Molecular Biology of Inflammatory Bowel Diseases

2011 ◽  
Vol 39 (4) ◽  
pp. 1057-1060 ◽  
Author(s):  
Anthony P. Corfield ◽  
Heather M. Wallace ◽  
Chris S.J. Probert
Keyword(s):  
Gastrointestinal Tract ◽  
Animal Models ◽  
Molecular Biology ◽  
Inflammatory Bowel Diseases ◽  
Susceptibility Genes ◽  
Adaptive Responses ◽  
Molecular Features ◽  
Disease Mechanisms ◽  
Bowel Diseases ◽  
Inflammatory Bowel

IBDs (inflammatory bowel diseases) are a group of diseases affecting the gastrointestinal tract. The diseases are multifactorial and cover genetic aspects: susceptibility genes, innate and adaptive responses to inflammation, and structure and efficacy of the mucosal protective barrier. Animal models of IBD have been developed to gain further knowledge of the disease mechanisms. These topics form an overlapping background to enable an improved understanding of the molecular features of these diseases. A series of articles is presented based on the topics covered at the Biochemical Society Focused Meeting The Molecular Biology of Inflammatory Bowel Diseases.

Neurocognitive and Perceptual Processing in Genetic Mouse Models of Schizophrenia: Emerging Lessons

2019 ◽  
Vol 25 (6) ◽  
pp. 597-619
Author(s):  
Anastasia Diamantopoulou ◽  
Joseph A. Gogos
Keyword(s):  
Animal Models ◽  
Psychiatric Disorders ◽  
Large Scale ◽  
Perceptual Processing ◽  
Great Promise ◽  
Biological Targets ◽  
The Past ◽  
Disease Mechanisms ◽  
Consistent Approach ◽  
Genetic Mouse Models

During the past two decades, the number of animal models of psychiatric disorders has grown exponentially. Of these, genetic animal models that are modeled after rare but highly penetrant mutations hold great promise for deciphering critical molecular, synaptic, and neurocircuitry deficits of major psychiatric disorders, such as schizophrenia. Animal models should aim to focus on core aspects rather than capture the entire human disease. In this context, animal models with strong etiological validity, where behavioral and neurophysiological phenotypes and the features of the disease being modeled are in unambiguous homology, are being used to dissect both elementary and complex cognitive and perceptual processing deficits present in psychiatric disorders at the level of neurocircuitry, shedding new light on critical disease mechanisms. Recent progress in neuroscience along with large-scale initiatives that propose a consistent approach in characterizing these deficits across different laboratories will further enhance the efficacy of these studies that will ultimately lead to identifying new biological targets for drug development.

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