Medical sciences widely use mouse models of human diseases as essential research tools to increase our understanding in the pathogenesis and pathophysiology of various diseases, and to search for cures. Despite the widespread use of mice as animal models of disease, in 2013, Seok et al. reported that mouse models poorly mimic human inflammatory diseases, such as severe burn injury, sepsis, and acute infection, in terms of gene expression (PNAS 2013, 110(9), 3507-3523), which has been cited more than 400 times since its publication only 18 months ago.
Their article led to great commotion, not only among scientists, but also in the popular mass media, including The New York Times and CBS News, reigniting controversy as to whether mouse models are effective for medical research. In response to the article, Dr. Francis S. Collins, director of the National Institutes of Health (NIH), revealed plans to develop "tissue chips" as alternatives to animal models of human disease.
Novel Transgenic Mouse Model of Chinese Charcot-Marie-Tooth Disease Type 2L Discovered
It was previously found that the K141N mutation in heat shock protein B8 (HSPB8) was responsible for the Charcot-Marie-Tooth disease type 2L in a large Chinese family
Advertisement
Professor Tsuyoshi Miyakawa from the Fujita Health University, and Associate Professor Keizo Takao, from the National Institute for Physiological Sciences in Japan, applied more appropriate and more sensitive methods for detecting similarities of gene expression patterns than that applied in the original PNAS paper to reanalyze the same datasets used in Seok et al. Professor Miyakawa said, "One of the authors of Seok et al. stated in an interview with the NY Times (*) that when the article was rejected by Nature and Science, they received comments such as 'It has to be wrong'. I had the same impression as the reviewers." Drs. Miyakawa and Takao then reanalyzed the data used in the Seok et al. paper, and found inadequate methods in the original analyses, leading them to a conclusion totally opposite to that of Seok et al.
Seok et al. compared the expression levels of genes that were altered in a particular human disease condition between humans and mice, regardless of whether the genes were changed in the mice. A comparison of the genomic response between humans and mice, including those genes altered in one species but not in another, obscures the correlation between homologous genes of humans and mice to nearly zero, as demonstrated by Seok et al.
![Health Problems of Software People]( "Health Problems of Software People")
About 70% of the employees identify "poor workplace set-up" as a cause of their problems. Software professionals may spend more than seven hours per day in front of a laptop or a desktop.
In Seok et al., comparison of the gene expression patterns between human burn and mouse models of burns, trauma, sepsis, and infection revealed Pearson's coefficient of correlation (R) that ranged from 0.14 to 0.28, and the percentage of genes whose expression changed in the same direction was 55% to 61%, indicating no correlation at all. In the present report, based on the same datasets used in Seok et al., the R values ranged from 0.36 to 0.59, and 77% to 93% of the genes changed in the same directions between the human disease and mouse model. Furthermore, in the present paper, the authors conducted more sophisticated non-biased statistical analyses of the similarity between gene sets of humans and mice utilizing the bioinformatics tool NextBio. Non-parametric ranking analysis using NextBio demonstrated that the pattern of the gene expression changes in mouse models was highly similar to that in human burn conditions with extraordinarily high confidence (overlap p-value = 1.2 x 10-35 - 6.5 x 10-11).
Many molecular pathways are commonly dysregulated in human diseases and mouse models. Numerous pathways, however, are not commonly affected in human diseases and mouse models. Focusing on the commonalities between human diseases and mouse models will allow us to derive useful information for studying the pathophysiology and pathogenesis of human diseases, and for developing treatments.
Source: Eurekalert
Health Problems of Software People
About 70% of the employees identify "poor workplace set-up" as a cause of their problems. Software professionals may spend more than seven hours per day in front of a laptop or a desktop.
Advertisement
In Seok et al., comparison of the gene expression patterns between human burn and mouse models of burns, trauma, sepsis, and infection revealed Pearson's coefficient of correlation (R) that ranged from 0.14 to 0.28, and the percentage of genes whose expression changed in the same direction was 55% to 61%, indicating no correlation at all. In the present report, based on the same datasets used in Seok et al., the R values ranged from 0.36 to 0.59, and 77% to 93% of the genes changed in the same directions between the human disease and mouse model. Furthermore, in the present paper, the authors conducted more sophisticated non-biased statistical analyses of the similarity between gene sets of humans and mice utilizing the bioinformatics tool NextBio. Non-parametric ranking analysis using NextBio demonstrated that the pattern of the gene expression changes in mouse models was highly similar to that in human burn conditions with extraordinarily high confidence (overlap p-value = 1.2 x 10-35 - 6.5 x 10-11).
Many molecular pathways are commonly dysregulated in human diseases and mouse models. Numerous pathways, however, are not commonly affected in human diseases and mouse models. Focusing on the commonalities between human diseases and mouse models will allow us to derive useful information for studying the pathophysiology and pathogenesis of human diseases, and for developing treatments.
Source: Eurekalert
Researchers Create Transgenic Mouse That can Synthesize Omega-3 and Omega-6 Fatty Acids
A transgenic mouse that can synthesize omega-3 and omega-6 essential fatty acids within its tissues while on a carbohydrate diet has been created.
Advertisement
 An Apple a Day Does Keep the Doctor Away, Confirms ResearchApples are as beneficial as taking statins, the cholesterol lowering drugs, confirms new research. Both can prevent or delay the number of deaths due to heart attack and stroke. | Advertisement
|
Advertisement
Latest Research News
Malaria parasites sync their molecular rhythms with the internal 24-hour clocks of their hosts, said researchers.
A latest research suggests that the quality of a person's post-work recovery in the evening can impact their mood when they resume work the next day.
Researchers are working on new strategies and solutions for sleep apnea to ward off a range of health risks including cognitive decline.
The scientists discovered that when the stem cells in the hair follicle are made softer, they have a higher chance of growing hair.
A combinatorial therapy provided promising beneficial results among people with ischemic stroke.