Engineering the Mouse Genome to Model Human Disease for Drug Discovery

2009 ◽  
pp. 55-77 ◽  
Author(s):  
Frank Koentgen ◽  
Gabriele Suess ◽  
Dieter Naf
Keyword(s):  
Drug Discovery ◽  
Human Disease ◽  
Mouse Genome

Monoallelic Expression of Pax5: A Paradigm for the Haploinsufficiency of Mammalian Pax Genes?

1999 ◽  
Vol 380 (6) ◽  
Author(s):  
S.L. Nutt ◽  
M. Busslinger
Keyword(s):  
Human Disease ◽  
Mouse Genome ◽  
Monoallelic Expression ◽  
Wild Type Allele ◽  
Loss Of Function ◽  
Wild Type ◽  
Type Allele ◽  
Pax Genes ◽  
Default State ◽  
Mammalian Genes

AbstractIt is generally assumed that most mammalian genes are transcribed from both alleles. Hence, the diploid state of the genome offers the advantage that a loss-of-function mutation in one allele can be compensated for by the remaining wild-type allele of the same gene. Indeed, the vast majority of human disease syndromes and engineered mutations in the mouse genome are recessive, indicating that recessiveness is the ‘default’ state. However, a minority of genes are semi-dominant, as heterozygous loss-of-function mutation in these genes leads to phenotypic abnormalities. This condition, known as haploinsufficiency, has been described for five of the nine mammalian

Zebrafish: An Emerging Model System for Human Disease and Drug Discovery

2007 ◽  
Vol 82 (1) ◽  
pp. 70-80 ◽  
Author(s):  
G Kari ◽  
U Rodeck ◽  
A P Dicker
Keyword(s):  
Drug Discovery ◽  
Human Disease ◽  
Model System

scholarly journals Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery

2012 ◽  
Vol 44 (3) ◽  
pp. 202 ◽  
Author(s):  
Jiho Jang ◽  
Jeong-Eun Yoo ◽  
Jeong-Ah Lee ◽  
Dongjin R. Lee ◽  
Ji Young Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Discovery ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Disease ◽  
Disease Modeling ◽  
Induced Pluripotent ◽  
Disease Specific

scholarly journals Mint Imperial: 16–18 December, 2002: Biochemical Society Meeting No. 678, Imperial College, London

2003 ◽  
Vol 25 (1) ◽  
pp. 25-27
Author(s):  
Gary Burd
Keyword(s):  
Drug Discovery ◽  
Human Disease ◽  
Imperial College ◽  
Cellular Proteins ◽  
Biological Processes ◽  
Biological Functions ◽  
Annual Symposium ◽  
Society Meeting ◽  
The World ◽  
Human Ageing

Ah… Christmas in London! But it seems the science was the biggest draw, as delegates came from around the world to listen to two medal lectures, and attend the Annual Symposium in honour of Alan Barrett, Proteases and the Regulation of Biological Processes. The Annual Symposium will be published as part of the Biochemical Society Symposia Series in the summer. Other colloquia included Polyamines and their Role in Human Disease, Human Ageing: from the Bench to the Clinic, Sulphotransferases in Glycobiology, Drug Discovery and Design, and Proteasome Interactions with Viral and Cellular Proteins. The Research Colloquium for young scientists was once again very popular, this time concentrating on Biological Functions of Sulphated Glycoproteins. Unusually, no dancing was observed at this meeting, but there was plenty of eating, with each colloquium having its own dinner.

scholarly journals Modelling familial dysautonomia in human induced pluripotent stem cells

2011 ◽  
Vol 366 (1575) ◽  
pp. 2286-2296 ◽  
Author(s):  
Gabsang Lee ◽  
Lorenz Studer
Keyword(s):  
Drug Discovery ◽  
Pluripotent Stem Cells ◽  
Human Disease ◽  
Genetic Disorder ◽  
Ips Cells ◽  
Familial Dysautonomia ◽  
Ips Cell ◽  
Modern Drug ◽  
Induced Pluripotent ◽  
Disease Specific

Induced pluripotent stem (iPS) cells have considerable promise as a novel tool for modelling human disease and for drug discovery. While the generation of disease-specific iPS cells has become routine, realizing the potential of iPS cells in disease modelling poses challenges at multiple fronts. Such challenges include selecting a suitable disease target, directing the fate of iPS cells into symptom-relevant cell populations, identifying disease-related phenotypes and showing reversibility of such phenotypes using genetic or pharmacological approaches. Finally, the system needs to be scalable for use in modern drug discovery. Here, we will discuss these points in the context of modelling familial dysautonomia (FD, Riley–Day syndrome, hereditary sensory and autonomic neuropathy III (HSAN-III)), a rare genetic disorder in the peripheral nervous system. We have demonstrated three disease-specific phenotypes in FD-iPS-derived cells that can be partially rescued by treating cells with the plant hormone kinetin. Here, we will discuss how to use FD-iPS cells further in high throughput drug discovery assays, in modelling disease severity and in performing mechanistic studies aimed at understanding disease pathogenesis. FD is a rare disease but represents an important testing ground for exploring the potential of iPS cell technology in modelling and treating human disease.

scholarly journals Analyzing of Molecular Networks for Human Diseases and Drug Discovery

2018 ◽  
Vol 18 (12) ◽  
pp. 1007-1014 ◽  
Author(s):  
Tong Hao ◽  
Qian Wang ◽  
Lingxuan Zhao ◽  
Dan Wu ◽  
Edwin Wang ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Biological Networks ◽  
Human Disease ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Topological Analysis ◽  
Molecular Networks ◽  
Protein Protein Interaction ◽  
Disease Research ◽  
Complex Functions

Molecular networks represent the interactions and relations of genes/proteins, and also encode molecular mechanisms of biological processes, development and diseases. Among the molecular networks, protein-protein Interaction Networks (PINs) have become effective platforms for uncovering the molecular mechanisms of diseases and drug discovery. PINs have been constructed for various organisms and utilized to solve many biological problems. In human, most proteins present their complex functions by interactions with other proteins, and the sum of these interactions represents the human protein interactome. Especially in the research on human disease and drugs, as an emerging tool, the PIN provides a platform to systematically explore the molecular complexities of specific diseases and the references for drug design. In this review, we summarized the commonly used approaches to aid disease research and drug discovery with PINs, including the network topological analysis, identification of novel pathways, drug targets and sub-network biomarkers for diseases. With the development of bioinformatic techniques and biological networks, PINs will play an increasingly important role in human disease research and drug discovery.

scholarly journals The Mouse Genome Database: Genotypes, Phenotypes, and Models of Human Disease

2012 ◽  
Vol 41 (D1) ◽  
pp. D885-D891 ◽  
Author(s):  
C. J. Bult ◽  
J. T. Eppig ◽  
J. A. Blake ◽  
J. A. Kadin ◽  
J. E. Richardson ◽  
...  
Keyword(s):  
Human Disease ◽  
Mouse Genome ◽  
Mouse Genome Database ◽  
Genome Database
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