scholarly journals Translating translational research: mouse models of human disease

2013 ◽  
Vol 10 (5) ◽  
pp. 373-374 ◽  
Author(s):  
Amanda M Burkhardt ◽  
Albert Zlotnik
2008 ◽  
Author(s):  
Martin Fenner

One of the opening lectures this Saturday of the International Congress of Genetics was held by Mario Capecchi. His talked was entitled Modeling human disease in the mouse: from cancer to neuropsychiatric disorders. In the first half he described his mouse model of synovial sarcoma. ...


2021 ◽  
Vol 15 (1) ◽  
pp. 8
Author(s):  
Rahman Ladak ◽  
Dana Philpott

With growing evidence that human disease is affected by the microbiota, many researchers have sought to modulate the microbiomes of mice to improve translational research. Altering their microbiomes, which are usually germ-free or specific pathogen-free, might allow mice to more accurately model human disease and hence produce more applicable findings. However, this has been difficult to apply to individual projects due to the disparity of explained methods and results. In this review, we first describe the immunological functions of the gut microbiota and the methods of altering mice microbiota, from transplantation route to age of transplantation to microbiota source. We then present an approach for how the gut microbiota might be considered when modelling human disease in mice. By organizing findings by type of disease - neurological, immunological, chronic inflammatory, and cancer - we propose that mouse models can be improved by considering the source of the microbiota, the presence or absence of certain microbial phyla, and by timing the transplantation during a physiologically relevant stage of development, such as the first five weeks of life.


2021 ◽  
Author(s):  
Aaron C. Ericsson ◽  
Craig L. Franklin

AbstractJust as the gut microbiota (GM) is now recognized as an integral mediator of environmental influences on human physiology, susceptibility to disease, and response to pharmacological intervention, so too does the GM of laboratory mice affect the phenotype of research using mouse models. Multiple experimental factors have been shown to affect the composition of the GM in research mice, as well as the model phenotype, suggesting that the GM represents a major component in experimental reproducibility. Moreover, several recent studies suggest that manipulation of the GM of laboratory mice can substantially improve the predictive power or translatability of data generated in mouse models to the human conditions under investigation. This review provides readers with information related to these various factors and practices, and recommendations regarding methods by which issues with poor reproducibility or translatability can be transformed into discoveries.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Paige B. Martin ◽  
Yu Kigoshi-Tansho ◽  
Roger B. Sher ◽  
Gianina Ravenscroft ◽  
Jennifer E. Stauffer ◽  
...  

Abstract A hallmark of neurodegeneration is defective protein quality control. The E3 ligase Listerin (LTN1/Ltn1) acts in a specialized protein quality control pathway—Ribosome-associated Quality Control (RQC)—by mediating proteolytic targeting of incomplete polypeptides produced by ribosome stalling, and Ltn1 mutation leads to neurodegeneration in mice. Whether neurodegeneration results from defective RQC and whether defective RQC contributes to human disease have remained unknown. Here we show that three independently-generated mouse models with mutations in a different component of the RQC complex, NEMF/Rqc2, develop progressive motor neuron degeneration. Equivalent mutations in yeast Rqc2 selectively interfere with its ability to modify aberrant translation products with C-terminal tails which assist with RQC-mediated protein degradation, suggesting a pathomechanism. Finally, we identify NEMF mutations expected to interfere with function in patients from seven families presenting juvenile neuromuscular disease. These uncover NEMF’s role in translational homeostasis in the nervous system and implicate RQC dysfunction in causing neurodegeneration.


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.


2006 ◽  
Vol 34 (4) ◽  
pp. 429-454 ◽  
Author(s):  
Nirmala Bhogal ◽  
Robert Combes
Keyword(s):  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Katarzyna I. Szczerkowska ◽  
Silvia Petrezselyova ◽  
Jiri Lindovsky ◽  
Marcela Palkova ◽  
Jan Dvorak ◽  
...  

2017 ◽  
Vol 118 (2) ◽  
pp. 845-854 ◽  
Author(s):  
Neal S. Peachey ◽  
Nazarul Hasan ◽  
Bernard FitzMaurice ◽  
Samantha Burrill ◽  
Gobinda Pangeni ◽  
...  

This article describes a mouse model of the human disease complete congenital stationary night blindness in which the mutation reduces but does not eliminate GRM6 expression and bipolar cell function, a phenotype distinct from that seen in other Grm6 mouse models.


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