Mouse Models for Human Diseases by Forward and Reverse Genetics

Author(s):  
Yoichi Gondo
2019 ◽  
Vol 35 (1) ◽  
Author(s):  
Daejin Hyung ◽  
Ann-Marie Mallon ◽  
Dong Soo Kyung ◽  
Soo Young Cho ◽  
Je Kyung Seong

Abstract Genetically engineered mouse models are used in high-throughput phenotyping screens to understand genotype-phenotype associations and their relevance to human diseases. However, not all mutant mouse lines with detectable phenotypes are associated with human diseases. Here, we propose the “Target gene selection system for Genetically engineered mouse models” (TarGo). Using a combination of human disease descriptions, network topology, and genotype-phenotype correlations, novel genes that are potentially related to human diseases are suggested. We constructed a gene interaction network using protein-protein interactions, molecular pathways, and co-expression data. Several repositories for human disease signatures were used to obtain information on human disease-related genes. We calculated disease- or phenotype-specific gene ranks using network topology and disease signatures. In conclusion, TarGo provides many novel features for gene function prediction.


Critical Care ◽  
2015 ◽  
Vol 19 (1) ◽  
Author(s):  
Tian Lin ◽  
Dayana Maita ◽  
Sujatha R Thundivalappil ◽  
Frank E Riley ◽  
Jasmin Hambsch ◽  
...  

2004 ◽  
Vol 16 (3) ◽  
pp. 349-360 ◽  
Author(s):  
Oleg Tarnavski ◽  
Julie R. McMullen ◽  
Martina Schinke ◽  
Qing Nie ◽  
Sekwon Kong ◽  
...  

Mouse models mimicking human diseases are important tools in trying to understand the underlying mechanisms of many disease states. Several surgical models have been described that mimic human myocardial infarction (MI) and pressure-overload-induced cardiac hypertrophy. However, there are very few detailed descriptions for performing these surgical techniques in mice. Consequently, the number of laboratories that are proficient in performing cardiac surgical procedures in mice has been limited. Microarray technologies measure the expression of thousands of genes simultaneously, allowing for the identification of genes and pathways that may potentially be involved in the disease process. The statistical analysis of microarray experiments is highly influenced by the amount of variability in the experiment. To keep the number of required independent biological replicates and the associated costs of the study to a minimum, it is critical to minimize experimental variability by optimizing the surgical procedures. The aim of this publication was to provide a detailed description of techniques required to perform mouse cardiac surgery, such that these models can be utilized for genomic studies. A description of three major surgical procedures has been provided: 1) aortic constriction, 2) pulmonary artery banding, 3) MI (including ischemia-reperfusion). Emphasis has been placed on technical procedures with the inclusion of thorough descriptions of all equipment and devices employed in surgery, as well as the application of such techniques for expression profiling studies. The cardiac surgical techniques described have been, and will continue to be, important for elucidating the molecular mechanisms of cardiac hypertrophy and failure with high-throughput technology.


2020 ◽  
Author(s):  
Sydney R. Coffey ◽  
Marissa Andrew ◽  
Heather Ging ◽  
Joseph Hamilton ◽  
Michael Flower ◽  
...  

AbstractExpanded trinucleotide repeats cause many human diseases, including Huntington’s disease (HD). Recent studies indicate that somatic instability of these repeats contributes to pathogenesis in several expansion disorders. We find that lowering huntingtin protein (HTT) levels reduces somatic instability of both the Htt and Atxn2 CAG tracts in knockin mouse models, and the HTT CAG tract in human iPSC-derived neurons, revealing an unexpected role for HTT in regulating somatic instability.


Science ◽  
2000 ◽  
Vol 289 (5476) ◽  
pp. 56a-56
Author(s):  
F. H. Kasten

2014 ◽  
pp. 163-177
Author(s):  
Lloyd A. Demetrius ◽  
Davide Malagoli
Keyword(s):  

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