Understanding our drugs and our diseases.

Proc Am Thorac Soc

Departments of Genetics and Genomics, Roche Palo Alto, Palo Alto, CA 94304, USA.

Published: July 2006

Analysis of mouse genetic models of human disease-associated traits has provided important insight into the pathogenesis of human disease. As one example, analysis of a murine genetic model of osteoporosis demonstrated that genetic variation within the 15-lipoxygenase (Alox15) gene affected peak bone mass, and that treatment with inhibitors of this enzyme improved bone mass and quality in rodent models. However, the method that has been used to analyze mouse genetic models is very time consuming, inefficient, and costly. To overcome these limitations, a computational method for analysis of mouse genetic models was developed that markedly accelerates the pace of genetic discovery. It was used to identify a genetic factor affecting the rate of metabolism of warfarin, an anticoagulant that is commonly used to treat clotting disorders. Computational analysis of a murine genetic model of narcotic drug withdrawal suggested a potential new approach for treatment of narcotic drug addiction. Thus, the results derived from computational mouse genetic analysis can suggest new treatment strategies, and can provide new information about currently available medicines.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658704PMC
http://dx.doi.org/10.1513/pats.200601-014AWDOI Listing

Publication Analysis

Top Keywords

mouse genetic
16
genetic models
12
genetic
9
analysis mouse
8
analysis murine
8
murine genetic
8
genetic model
8
bone mass
8
narcotic drug
8
analysis
5

Similar Publications

DYT-THAP1 dystonia is a monogenetic form of dystonia, a movement disorder characterized by the involuntary co-contraction of agonistic and antagonistic muscles. The disease is caused by mutations in the THAP1 gene, although the precise mechanisms by which these mutations contribute to the pathophysiology of dystonia remain unclear. The incomplete penetrance of DYT-THAP1 dystonia, estimated at 40 to 60 %, suggests that an environmental trigger may be required for the manifestation of the disease in genetically predisposed individuals.

View Article and Find Full Text PDF

Background & Aims: Metabolic dysfunction-associated steatotic liver (MASLD) progression is driven by chronic inflammation and fibrosis, largely influenced by Kupffer cell (KC) dynamics, particularly replenishment of pro-inflammatory monocyte-derived KCs (MoKCs) due to increased death of embryo-derived KCs. Adenosine A3 receptor (A3AR) plays a key role in regulating metabolism and immune responses, making it a promising therapeutic target. This study aimed to investigate the impact of selective A3AR antagonism for regulation of replenished MoKCs, thereby improving MASLD.

View Article and Find Full Text PDF

Signaling in autism: Relevance to nutrients and sex.

Curr Opin Neurobiol

December 2024

Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan, ROC. Electronic address:

Autism spectrum disorders (ASD) are substantially heterogeneous neuropsychiatric conditions with over a thousand associated genetic factors and various environmental influences, such as infection and nutrition. Additionally, males are four times more likely than females to be affected. This heterogeneity underscores the need to uncover common molecular features within ASD.

View Article and Find Full Text PDF

The PA-X host shutoff site 100 V exerts a contrary effect on viral fitness of the highly pathogenic H7N9 influenza A virus in mice and chickens.

Virulence

December 2025

Key Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou, China.

Several viruses, including influenza A virus (IAV), encode viral factors to hijack cellular RNA biogenesis processes to direct the degradation of host mRNAs, termed "host shutoff." Host shutoff enables viruses to simultaneously reduce antiviral responses and provides preferential access for viral mRNAs to cellular translation machinery. IAV PA-X is one of these factors that selectively shuts off the global host genes.

View Article and Find Full Text PDF

Polymer based nanoformulations offer substantial prospects for efficacious chemotherapy delivery. Here, we developed a pH-responsive polymeric nanoparticle based on acidosis-triggered breakdown of boronic ester linkers. A biocompatible hyaluronic acid (HA) matrix served as a substrate for carrying a doxorubicin (DOX) prodrug which also possesses natural affinity for CD44 cells.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!