scholarly journals Developmental gene expression differences between humans and mammalian models

2019 ◽  
Author(s):  
Margarida Cardoso-Moreira ◽  
Britta Velten ◽  
Matthew Mort ◽  
David N. Cooper ◽  
Wolfgang Huber ◽  
...  

AbstractIdentifying the molecular programs underlying human organ development and how they differ from those in model species will advance our understanding of human health and disease. Developmental gene expression profiles provide a window into the genes underlying organ development as well as a direct means to compare them across species. We use a transcriptomic resource for mammalian organ development to characterize the temporal profiles of human genes associated with distinct disease classes and to determine, for each human gene, the similarity of its spatiotemporal expression with its orthologs in rhesus macaque, mouse, rat and rabbit. We find that half of human genes differ from their mouse orthologs in their temporal trajectories. These include more than 200 disease genes associated with brain, heart and liver disease, for which mouse models should undergo extra scrutiny. We provide a new resource that evaluates for every human gene its suitability to be modeled in different mammalian species.

BMC Genomics ◽  
2009 ◽  
Vol 10 (1) ◽  
pp. 128 ◽  
Author(s):  
Geoffrey N Gobert ◽  
Luke Moertel ◽  
Paul J Brindley ◽  
Donald P McManus

2015 ◽  
Vol 37 (3) ◽  
pp. 203-214 ◽  
Author(s):  
Joshua L. Cohen ◽  
Matthew E. Glover ◽  
Phyllis C. Pugh ◽  
Andrew D. Fant ◽  
Rebecca K. Simmons ◽  
...  

The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high versus low behavioral response to novelty and found that high-reactive (bred high-responder, bHR) rats displayed greater risk-taking, impulsivity and aggression relative to low-reactive (bred low-responder, bLR) rats, which showed high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable, but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior to the brain development and emotional behavior of bLR offspring. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine the effects on the following: (1) developmental gene expression in the hippocampus and amygdala and (2) adult anxiety/depression-like behavior. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus), reduced adult anxiety and enhanced social interaction. Our findings illustrate how an early-life manipulation such as cross-fostering changes the brain's developmental trajectory and ultimately impacts adult behavior. Moreover, while earlier studies highlighted hippocampal differences contributing to the bHR/bLR phenotypes, our results point to a role of the amygdala as well. Future work will pursue genetic and cellular mechanisms within the amygdala that contribute to bHR/bLR behavior either at baseline or following environmental manipulations.


Burns ◽  
2019 ◽  
Vol 45 (2) ◽  
pp. 387-397
Author(s):  
Dan Wu ◽  
Ming Zhou ◽  
Liang Li ◽  
Xiangfeng Leng ◽  
Zheng Zhang ◽  
...  

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