Story ideas from the Journal of Lipid Research

March 06, 2008

The Complexity of Disease Phenotypes

Animal models have been invaluable in understanding how gene mutations physically affect a complex organism. However, as vividly illustrated in a new research study examining mice with a metabolic disease, the same mutation in the same species can produce wildly variable results.

Niemann-Pick type C (NPC) disease is a rare genetic condition brought on by a mutation in one protein, NPC1, which helps shuttle cholesterol out of a cell compartment called the lysosome. As a result, cholesterol accumulates in virtually every tissue in the body, causing widespread organ dysfunction and death.

John Dietschy and colleagues evaluated how factors like genetic background, additional mutations, and environmental influences affected the lifespan of a mouse model of NBC. Overall, the lifespan of different npc1-/- mice ranged from 50-130 days, and even simple differences such as the host colony (same strain, just different location of breeding), or slight alterations in diet affected the average lifespan.

These studies highlight just how complex a 'simple' genetic disease really is, and that such variability should be carefully considered when designing animal experiments or interpreting results. It is particularly important, Dietschy and colleagues note, to use these animal models to carefully differentiate the non-specific environmental and genetic effects on lifespan from treatments that have a direct effect on the genetic abnormality present in the disease and thus may promote survival.
-end-
Corresponding Author: John M. Dietschy, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX; Phone: 214-648-2150; email: john.dietschy@utsouthwestern.edu

American Society for Biochemistry and Molecular Biology

Related Metabolic Disease Articles from Brightsurf:

Brain astrocytes show metabolic alterations in Parkinson's disease
A new study using induced pluripotent stem cell (iPSC) technology links astrocyte dysfunction to Parkinson's disease (PD) pathology.

Metabolic fossils from the origin of life
Since the origin of life, metabolic networks provide cells with nutrition and energy.

Testosterone levels affect risk of metabolic disease and cancers
Having genetically higher testosterone levels increases the risk of metabolic diseases such as type 2 diabetes in women, while reducing the risk in men.

Perinatal exposure to flame retardant alters epigenome, predisposing metabolic disease
A UMass Amherst study showed that environmentally relevant exposure to polybrominated diphenyl ether (PBDE), a brominated flame retardant, through the umbilical cord and breast milk permanently changed liver metabolism in rats.

Little-known protein appears to play important role in obesity and metabolic disease
With unexpected findings about a protein that's highly expressed in fat tissue, scientists at Scripps Research have opened the door to critical new understandings about obesity and metabolism.

Metabolic syndrome: New use for an old drug
The discovery, described in a study by Cosbi and Cimec of the University of Trento published today in Nature Communications, confirms the effectiveness of repurposing, the new frontier of pharmacological research.

New finding offers possibility for preventing age-related metabolic disease
A study by researchers at Yale has uncovered why belly fat surrounding organs increases as people age, a finding that could offer new treatment possibilities for improving metabolic health, thereby reducing the likelihood for diseases like diabetes and atherosclerosis that stem from inflammation.

Treatment of metabolic dysfunction could be a potential therapy for Alzheimer's disease
A team of researchers led by Yale-NUS College has found evidence that metabolic dysfunction is a primary cause of Alzheimer's disease.

Metabolic discovery may help in fight against heart disease, diabetes
Researchers at Cornell University have uncovered a key step in how the human body metabolizes sugar, which could lead to better treatment and prevention of heart disease, obesity and Type 2 diabetes.

Clemson researchers tie metabolic enzyme to obesity and fatty liver disease
Researchers from Clemson University's Environmental Toxicology Program have published research connecting an enzyme associated with detoxification to obesity and fatty liver disease, especially in males.

Read More: Metabolic Disease News and Metabolic Disease Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.