2022 updates to the Rat Genome Database: a Findable, Accessible, Interoperable, and Reusable (FAIR) resource

Genetics, Journal Year: 2023, Volume and Issue: 224(1)

Published: March 17, 2023

Abstract The Rat Genome Database (RGD, https://rgd.mcw.edu) has evolved from simply a resource for rat genetic markers, maps, and genes, by adding multiple genomic data types extensive disease phenotype annotations developing tools to effectively mine, analyze, visualize the available data, empower investigators in their hypothesis-driven research. Leveraging its robust flexible infrastructure, RGD added human eight other model organisms (mouse, 13-lined ground squirrel, chinchilla, naked mole-rat, dog, pig, African green monkey/vervet, bonobo) besides enhance translational aspect. This article presents an overview of database with most recent additions RGD’s genome, variant, quantitative data. We also briefly introduce Virtual Comparative Map (VCMap), updated tool that explores synteny between species as improvement suite tools, followed discussion regarding refinements existing PhenoMiner assists researchers finding comparing across strains. Collectively, focuses on providing continuously improving, consistent, high-quality while advancing reproducibility fulfilling Findable, Accessible, Interoperable, Reusable (FAIR) principles.

Language: Английский

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Animal Models of Human Disease

Published: April 17, 2024

The crucial role of animal models in biomedical research calls for philosophical investigation how and whether knowledge about human diseases can be gained by studying other species. This Element delves into the selection construction to serve as preclinical substitutes patients. It explores multifaceted roles fulfil translational boundaries between humans animals are negotiated this process. book also covers persistent challenges that have sparked debates across scientific, philosophical, public arenas regarding limitations future models. Among tensions standardization variation medicine, well strategies aiming reduce recapitulate biological complexity. Finally, examines prospects replacing with animal-free methods. demonstrates why modeling should interest philosophers, social scientists, scientists alike.

Language: Английский

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Protecting Human and Animal Health: The Road from Animal Models to New Approach Methods

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(2), P. 251 - 266

Published: Jan. 5, 2024

Animals and animal models have been invaluable for our current understanding of human biology, including physiology, pharmacology, biochemistry, disease pathology. However, there are increasing concerns with continued use animals in basic biomedical, pharmacological, regulatory research to provide safety assessments drugs chemicals. There that do not sufficient information on toxicity and/or efficacy protect the target population, so scientists utilizing principles replacement, reduction, refinement (the 3Rs) development application new approach methods (NAMs). NAMs any technology, methodology, approach, or assay used understand effects mechanisms chemicals, specific focus applying 3Rs. Although progress has made several areas NAMs, complete replacement is yet attainable. The road requires additional development, increased use, and, decision making, usually formal validation. Moreover, it likely will require multiple assays ensure biologic coverage. purpose this manuscript a balanced view state as approaches safety, efficacy, testing all needed nor but each can elucidate key pieces puzzle biology contribute goal protecting health.

Significance Statement

Data from traditional studies predominantly inform health efficacy. unlikely be able replaced, advancement (NAMs), possible sometime future, an important component by which discovery, chemicals conducted decisions made.

Language: Английский

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Deletion of IRS-1 leads to growth failure and insulin resistance with downregulation of liver and muscle insulin signaling in rats

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 8, 2025

Insulin receptor substrate (IRS)-1 and IRS-2 are major molecules that transduce signals from insulin insulin-like growth factor-I receptors. The physiological functions of these proteins have been intensively investigated in mice, while little is known other animals. Our previous study showed the disruption impairs body but not glucose tolerance or sensitivity rats, which led us to hypothesize IRS-1 plays more pivotal roles than IRS-2. Here, we created knockout (KO) rats elucidate rats. weight KO at birth was lower wild-type (WT) littermates, postnatal severely impaired. Compared with WT displayed resistance maintained euglycemia because compensatory hyperinsulinemia. In addition, despite increased activity insulin-stimulated IRS-2-associated phosphatidylinositol-3 kinase (PI3K), insulin-induced phosphorylation kinases downstream PI3K suppressed liver skeletal muscle Taken together, results indicate essential for normal glucose-lowering effects insulin. appears be important

Language: Английский

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Advances in Genome Editing and Application to the Generation of Genetically Modified Rat Models

Frontiers in Genetics, Journal Year: 2021, Volume and Issue: 12

Published: April 20, 2021

The rat has been extensively used as a small animal model. Many genetically engineered models have emerged in the last two decades, and advent of gene-specific nucleases accelerated their generation recent years. This review covers techniques advances to generate lines application development more broadly, such conditional knockouts reporter gene strains. In addition, genome-editing that remain be explored are discussed. also focuses particularly on areas which extensive work done: human genetic diseases immune system analysis. Models thoroughly described these highlight competitive advantages over available corresponding mouse versions. objective this is provide comprehensive description potential for addressing specific scientific questions characterize best genome-engineering tools developing new projects.

Language: Английский

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Calcium Hydroxyapatite in Its Different Forms in Skin Tissue Repair: A Literature Review

Surgeries, Journal Year: 2024, Volume and Issue: 5(3), P. 640 - 659

Published: Aug. 9, 2024

The skin is crucial for homeostasis and body defense, requiring quick healing to maintain internal balance. Initially used bone repair, calcium hydroxyapatite (HAp) now being studied soft tissue engineering. This literature review investigated HAp’s role in repair through searches on PubMed, Scopus (Elsevier), Science Direct, Springer Link, Google Scholar databases without time restrictions, using keywords “hydroxyapatite AND wound” repair”. Inclusion criteria encompassed vivo studies humans animals, English publications, full access, sufficient data repair. Exclusions included duplicates, unrelated articles, editor letters, reviews, comments, conference abstracts, dissertations, theses. Out of the 472 articles initially identified, 139 met inclusion criteria, with 21 focusing HAp Findings indicate that nano-HAp regeneration are promising, especially when combined other biomaterials, offering antimicrobial anti-inflammatory benefits stimulating angiogenesis. suggests their potential application dermatology, surgery, dentistry, extending versatility from hard tissues enhancing critical properties accelerating healing.

Language: Английский

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Rat Models of Hormone Receptor-Positive Breast Cancer

Journal of Mammary Gland Biology and Neoplasia, Journal Year: 2024, Volume and Issue: 29(1)

Published: June 24, 2024

Abstract Hormone receptor-positive (HR + ) breast cancer (BC) is the most common type of among women worldwide, accounting for 70–80% all invasive cases. Patients with HR BC are commonly treated endocrine therapy, but intrinsic or acquired resistance a frequent problem, making focal point intense research. Despite this, malignancy still lacks adequate in vitro and vivo models study its initiation progression as well response to therapy. No mouse that fully mimic human disease available, however rat mammary tumor pose promising alternative overcome this limitation. Compared mice, rats more similar humans terms gland architecture, ductal origin neoplastic lesions hormone dependency status. Moreover, can develop spontaneous induced tumors resemble BC. To date, six different types have been established. These include spontaneous, carcinogen-induced, transplantation, hormone-induced, radiation-induced genetically engineered models. Each model has distinct advantages, disadvantages utility studying This review provides comprehensive overview published date.

Language: Английский

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Mouse models of fragile X-related disorders

Disease Models & Mechanisms, Journal Year: 2023, Volume and Issue: 16(2)

Published: Jan. 24, 2023

ABSTRACT The fragile X-related disorders are an important group of hereditary that caused by expanded CGG repeats in the 5′ untranslated region FMR1 gene or mutations coding sequence this gene. Two categories pathological associated with these disorders, full mutation alleles and shorter premutation alleles. Individuals develop X syndrome, which causes autism intellectual disability, whereas those alleles, have expansions, can X-associated tremor/ataxia a progressive neurodegenerative disease. Thus, manifest as neurodevelopmental depending on size repeat expansion. Here, we review mouse models discuss how they informed our understanding disorders. We also assess translational value for developing rational targeted therapies disability

Language: Английский

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The evolutionary history of wild and domestic brown rats ( Rattus norvegicus )

Science, Journal Year: 2024, Volume and Issue: 385(6715), P. 1292 - 1297

Published: Sept. 19, 2024

The brown rat ( Rattus norvegicus ) occupies nearly every terrestrial habitat with a human presence and is one of our most important model organisms. Despite this prevalence, gaps remain in understanding the evolution commensalism, their global dispersal, mechanisms underlying contemporary adaptations to diverse environments. In Review, we explore recent advances evolutionary history rats discuss key challenges, including finding accurately dating historical specimens, disentangling histories multiple domestication events, synthesizing functional variation wild populations development laboratory strains. Advances zooarchaeology population genomics will usher new golden age research on biology rats, positive feedbacks use as biomedical models.

Language: Английский

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Animal Models in Human Adenovirus Research

Biology, Journal Year: 2021, Volume and Issue: 10(12), P. 1253 - 1253

Published: Dec. 1, 2021

Human adenovirus (HAdV) infections cause a wide variety of clinical symptoms, ranging from mild upper respiratory tract disease to lethal outcomes, particularly in immunocompromised individuals. To date, neither widely available vaccines nor approved antiadenoviral compounds are efficiently deal with HAdV infections. Thus, there is need thoroughly understand HAdV-induced disease, and for the development preclinical evaluation therapeutics and/or vaccines, consequently suitable standardizable vitro systems animal models. Current models study pathogenesis, persistence, tumorigenesis include rodents such as Syrian hamsters, mice, cotton rats, well rabbits. In addition, few recent studies on other species, pigs tree shrews, reported promising data. These mimic (aspects of) pathological changes humans and, although they relevant, an ideal model has yet be developed. This review summarizes infection comprehensive descriptions virus-induced pathogenesis different species. We also elaborate rodent how contributed insights into adenovirus-induced cell transformation cancer.

Language: Английский

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