Author : Karen Louise Svenson
Publisher :
Page : 132 pages
File Size : 31,45 MB
Release : 2008
Category :
ISBN : 9789036736282
Author : Qingbo Xu
Publisher : Wiley
Page : 402 pages
File Size : 43,81 MB
Release : 2006-08-04
Category : Science
ISBN : 0470028785
The availability of well-defined genetic strains and the ability to create transgenic and knockout mice makes mouse models extremely valuable biomedical tools. Their suitability as an experimental system for cardiovascular research depends on the individual investigator’s ability to manipulate the mice surgically. Many mouse models require microsurgical techniques, which hitherto could not be performed without practical training. This comprehensive handbook enables scientists to develop these models in their own laboratories. A Handbook of Mouse Models of Cardiovascular Disease is the first book to address pathology in mouse models of heart disease, providing the reader with essential information on technical assays in artificially created models. It includes background information on individual cardiovascular diseases, describes detailed methods and materials used for establishing each mouse model, discusses the problems that may appear in the experiments, and provides examples of applications of the model. A Handbook of Mouse Models of Cardiovascular Disease: Describes mouse models of all important cardiovascular diseases, including atherosclerosis, atrial fibrillation and thrombosis Features videos of key experimental procedures on the accompanying CD, allowing researchers to learn the techniques by directly watching the whole operational procedure Describes how to establish each experimental model with detailed protocols and tips on dealing with common operational problems Highlights potential applications of each model in areas such as pathogenesis, gene transfer, therapy and pathophysiology This handbook is an invaluable resource for researchers in cardiovascular disease, pathology, physiology, interested in the mechanism of vascular disorders and therapeutic approaches. It is also relevant to clinicians seeking to understand the pathology of cardiovascular disease and the rationale for interventions, and of interest to the pharmaceutical industry and all those involved in drug discovery/development for cardiovascular disease.
Author : Qingbo Xu
Publisher :
Page : 360 pages
File Size : 27,89 MB
Release : 2006-10-28
Category : Science
ISBN : 9780470028797
The availability of well-defined genetic strains and the ability to create transgenic and knockout mice makes mouse models extremely valuable biomedical tools. Their suitability as an experimental system for cardiovascular research depends on the individual investigator’s ability to manipulate the mice surgically. Many mouse models require microsurgical techniques, which hitherto could not be performed without practical training. This comprehensive handbook will enable scientists to develop these models in their own laboratories. It contains detailed advice on the issues that investigators need to consider before starting their experiments. It then provides essential information about experimental procedures, specific instruments and technical knowledge and will prove an indispensable guide to all scientists planning to work with these mouse models. This book includes a brief introduction to each disease, followed by a detailed description of the methods and materials used to establish the relevant mouse model. Each chapter has been written by an expert familiar with that system, who provides helpful discussion of the problems that may be encountered and examples of applications of the model. Importantly, each technique is clearly illustrated on the accompanying CD, so that researchers can observe the operational procedures directly. With coverage of all the major mouse models of cardiovascular disease, this book may be used to obtain a broad overview of commonly used methods and, more importantly, as a comprehensive source of detailed information on the development and study of such models. It will prove essential reading to all those working on experimental animal models of cardiovascular disease, from students to independent investigators.
Author : Gabriele Proetzel
Publisher : Humana Press
Page : 0 pages
File Size : 43,58 MB
Release : 2009-12-17
Category : Medical
ISBN : 9781607610571
As the drug discovery process shifts more and more toward specifically targeting pathways and molecules, model systems continue to increase in importance, and the mouse, with its versatility, ease of use, and remarkable similarity to the human genome, has clearly risen to the forefront of animal model studies. In Mouse Models for Drug Discovery: Methods and Protocols, experts in the field present some background for those less familiar with mice as experimental model platforms as well as a collection of techniques involving general methods as well as specific disease topics such as type 1 and 2 diabetes, cardiovascular disease, arthritis, skin disorders, cancer, the use of behavioral models for depression and anxiety, neurodegenerative diseases, neuromuscular diseases, and infectious diseases. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easy-to-use, Mouse Models for Drug Discovery: Methods and Protocols will stimulate those not familiar with the power of the mouse and its potential for the drug discovery process, and it will encourage the development of new models and new ways to utilize existing models in order to further the use of this dynamic animal in this vital field.
Author : J. O. S. Cleary
Publisher :
Page : pages
File Size : 45,51 MB
Release : 2012
Category :
ISBN :
With the completion of the human genome sequence in 2003, efforts have shifted towards elucidating gene function. Such phenotypic investigations are aided by advances in techniques for genetic modification of mice, with whom we share ~99% of genes. Mice are key models for both examination of basic gene function and translational study of human conditions. Furthering these efforts, ambitious programmes are underway to produce knockout mice for the ~25,000 mouse genes. In the coming years, methods to rapidly phenotype mouse morphology will be in great demand. This thesis demonstrates the development of non-invasive microscopic magnetic resonance imaging (\muMRI) methods for high-resolution ex-vivo phenotyping of mouse embryo and mouse brain morphology. It then goes on to show the application of computational atlasing techniques to these datasets, enabling automated analysis of phenotype. First, the issue of image quality in high-throughput embryo MRI was addressed. After investigating preparation and imaging parameters, substantial gains in signal- and contrast-to-noise were achieved. This protocol was applied to a study of Chd7+/- mice (a model of CHARGE syndrome), identifying cardiac defects. Combining this protocol with automated segmentation-propagation techniques, phenotypic differences were shown between three groups of mice in a volumetric analysis involving a number of organ systems. Focussing on the mouse brain, the optimal preparation and imaging parameters to maximise image quality and structural contrast were investigated, producing a high-resolution in-skull imaging protocol. Enhanced delineation of hippocampal and cerebellar structures was observed, correlating well to detailed histological comparisons. Subsequently this protocol was applied to a phenotypic investigation of the Tc1 model of Down syndrome. Using both visual inspection and automated, tensor based morphometry, novel phenotypic findings were identified in brain and inner ear structures. It is hoped that a combination of \muMRI with computational analysis techniques, as presented in this work, may help ease the burden of current phenotyping efforts.
Author : Stephen Chang
Publisher :
Page : pages
File Size : 23,52 MB
Release : 2020
Category :
ISBN :
Due to differences in cardiac structure and function, it has become increasingly clear that many aspects of cardiovascular anatomy, physiology, biochemistry, and disease are not well modeled in mice. This has spurred a search for new model organisms with the practical advantages of mice but that more closely mimic human biology and disease. This study examines mouse lemur (Microcebus species) -- the world's smallest, most prolific, and among the most abundant non-human primates -- and the cheapest and easiest to maintain, as such a model. Little is known of lemur cardiovascular physiology, cell types, or pathology. This thesis describes the characterization of normal cardiac anatomy and histology, and baseline values for heart rate, cholesterol/lipids, and cardiac waveform by electrocardiography (ECG). It also describes the development of a single cell RNA-sequencing and analysis pipeline for Microcebus murinus that provided genome-wide expression profiles of thousands of cardiac cells. Computational clustering of these transcriptomic profiles, and analysis of cluster-specific expression patterns of mouse lemur orthologues of canonical markers of human and mouse cardiac cell types, identified all major and many minor cardiac cell types in mouse lemur, including several exceedingly rare cell types. To begin to identify cardiac diseases in mouse lemur, a portable 3-lead ECG monitoring device was used to screen ~300 laboratory Microcebus murinus mouse lemurs and ~100 wild Microcebus rufus and a new species of mouse lemurs in Ranomafana National Park in Madagascar. This identified 20 naturally-occurring ECG variants in 170 affected lab and wild animals, with all identified variants resembling known human ECG variants including 8 major cardiac arrhythmias and pathologies plus 7 additional potentially pathological variants. The screen uncovered the first cases of heart disease in lemurs. One is atrial fibrillation, the most common arrhythmia in humans. Another is mouse lemur sick sinus syndrome (SSS), with episodic bradycardia resembling human SSS, whose familial forms arise from mutations in cardiac ion channel genes HCN4 or SCN5A. Both of these mouse lemur pathologic arrythmias show familial clustering, consistent with a genetic origin. The family pedigrees can now be used to determine the inheritance pattern of these diseases, map the underlying disease genes, and sequence the disease loci to identify the causative mutation. The results establish the mouse lemur as the first systematic, high-throughput primate genetic model for cardiovascular physiology and disease, and reveal human-like cardiac cell types and diseases. The approach uncovered naturally-occurring cardiac diseases that have not been found in mice. Furthermore, the strategy outlined here serves as a paradigm for identifying and studying physiological and behavioral traits and diseases beyond the cardiovascular system in this new primate genetic model organism.
Author : Michael Shenghan Yu
Publisher :
Page : 119 pages
File Size : 29,55 MB
Release : 2018
Category :
ISBN :
Here we describe an original phenotypical platform to identify novel regulators of cardiac rhythm and arrhythmia-causing genes in hPSC-derived atrial-like cardiomyocytes (hPSC-ACM).The system applies well-characterized atrial subtype cardiomyocytes generated from Id1-induced cardiogenic mesoderm progenitors. The platform integrates automated high-throughput/high-content kinetic imaging system with fluorescence quantification and single-cell resolution trace analysis algorithm to retrieve physiological metrics of hPSC-ACMs biology. This generic platform enables the high-throughput phenotypical evaluation of functional genomics and small molecules on cardiac physiological parameters in both healthy or disease contexts. The system is also functionally validated with genes previously associated with atrial fibrillation (AF) and confirmed the occurrence of arrhythmia-like activity in hPSC-ACMs induced by siRNA-mediated knockdown of the genes along with AF-associated perturbagens. We then modeled and categorized different arrhythmia-subtypes arise from distinct molecular events. Overall, the hPSC-ACM differentiation protocol provides a robust resource to study atrial-specific cardiac diseases and development; the platform and single-cell analysis generate higher resolutions of information without sacrificing the throughout; and the modeling and characterization of arrhythmia-like activity shed light upon this unique approach to identify novel regulators of cardiac rhythm and arrhythmia-causing genes in an atrial-specific manner.
Author : Institute of Medicine
Publisher : National Academies Press
Page : 354 pages
File Size : 31,50 MB
Release : 2012-09-13
Category : Science
ISBN : 0309224187
Technologies collectively called omics enable simultaneous measurement of an enormous number of biomolecules; for example, genomics investigates thousands of DNA sequences, and proteomics examines large numbers of proteins. Scientists are using these technologies to develop innovative tests to detect disease and to predict a patient's likelihood of responding to specific drugs. Following a recent case involving premature use of omics-based tests in cancer clinical trials at Duke University, the NCI requested that the IOM establish a committee to recommend ways to strengthen omics-based test development and evaluation. This report identifies best practices to enhance development, evaluation, and translation of omics-based tests while simultaneously reinforcing steps to ensure that these tests are appropriately assessed for scientific validity before they are used to guide patient treatment in clinical trials.
Author : Carolyn A. Staton
Publisher : John Wiley & Sons
Page : 410 pages
File Size : 50,49 MB
Release : 2007-01-11
Category : Medical
ISBN : 047002934X
Angiogenesis, the development of new blood vessels from the existing vasculature, is essential for physiological growth and over 18,000 research articles have been published describing the role of angiogenesis in over 70 different diseases, including cancer, diabetic retinopathy, rheumatoid arthritis and psoriasis. One of the most important technical challenges in such studies has been finding suitable methods for assessing the effects of regulators of eh angiogenic response. While increasing numbers of angiogenesis assays are being described both in vitro and in vivo, it is often still necessary to use a combination of assays to identify the cellular and molecular events in angiogenesis and the full range of effects of a given test protein. Although the endothelial cell - its migration, proliferation, differentiation and structural rearrangement - is central to the angiogenic process, it is not the only cell type involved. the supporting cells, the extracellular matrix and the circulating blood with its cellular and humoral components also contribute. In this book, experts in the use of a diverse range of assays outline key components of these and give a critical appraisal of their strengths and weaknesses. Examples include assays for the proliferation, migration and differentiation of endothelial cells in vitro, vessel outgrowth from organ cultures, assessment of endothelial and mural cell interactions, and such in vivo assays as the chick chorioallantoic membrane, zebrafish, corneal, chamber and tumour angiogenesis models. These are followed by a critical analysis of the biological end-points currently being used in clinical trials to assess the clinical efficacy of anti-angiogenic drugs, which leads into a discussion of the direction future studies should take. This valuable book is of interest to research scientists currently working on angiogenesis in both the academic community and in the biotechnology and pharmaceutical industries. Relevant disciplines include cell and molecular biology, oncology, cardiovascular research, biotechnology, pharmacology, pathology and physiology.
Author : Benoit G. Bruneau
Publisher :
Page : pages
File Size : 20,76 MB
Release : 2020
Category : Congenital heart disease
ISBN : 9781621823599
"Development of the heart is a complex process and can lead to serious congenital disease if the process goes awry. This book provides a detailed description of the cell lineages involved in heart development and how their migration and morphogenesis are controlled. It also examines the genetic and environmental bases for congenital heart disease and how model systems are revealing more about the processes involved"--
