Effects of gestational alcohol exposure

Though it is well known that gestational exposure to alcohol can cause offspring to develop physical, behavioral or learning problems, the molecular mechanisms underlying fetal alcohol spectrum disorders remain unknown. Now researchers have shown that gestational exposure to ethanol can affect adult phenotype by altering the epigenotype, or the pattern of gene expression, of the early mouse embryo (PLoS Genet. 6, e1000811; 2010).

Suyinn Chong of the Queensland Institute of Medical Research (Herston, Australia) and colleagues used a reporter allele, called Agouti viable yellow (Avy), whose expression is linked to its epigenetic state. The activity of Avy varies in genetically identical mice, resulting in coat colors ranging from butter yellow to agouti. Female mice were allowed to mate, and then for 8 days after fertilization, some were given free access to 10% ethanol instead of water.

Exposure to alcohol increased the probability of transcriptional silencing of the Avy allele in offspring, meaning that the mice exposed to ethanol gave birth to more mice with agouti-colored coats. Additionally, some of the offspring that had been exposed to alcohol had features resembling those of fetal alcohol syndromes. The authors plan to use this mouse model to further study the consequences of gestational alcohol exposure at the molecular level.

Skin grafts regulate blood pressure in mice

In a step towards developing skin graft therapies for humans, researchers have shown that they can use bioengineered human skin to regulate and decrease blood pressure in mice (Proc. Natl. Acad. Sci. USA 107, 1178–1183; 2010). The skin grafts are engineered to produce certain molecules and deliver them to the bloodstream. By changing which molecules they produce, skin grafts could potentially be used to treat other medical conditions.

In the current study, Jonathan Vogel of the National Institutes of Health (Bethesda, MD) and colleagues engineered human skin cells to express atrial natriuretic peptide (ANP), a hormone that decreases blood pressure. They attached these grafts to mice and measured the mice's plasma levels of human ANP 2, 4 and 7 months later. ANP levels were significantly higher in treated mice than in control mice (which received grafts that did not express ANP). The patches also lowered blood pressure in mice fed a normal diet and prevented high blood pressure in mice fed a high-salt diet.

The researchers think this approach could be used to develop systemic disease therapies. Future studies will need to address whether the technology can be scaled up for use in humans, as well as how long the grafts can effectively deliver their products.

VLP vaccine for Chikungunya

Chikungunya virus is a mosquito-borne infectious disease that causes severe arthritis. Since re-emerging in 2004, it has infected millions of people. Attempts to develop vaccines had only limited success until recently, when researchers developed a vaccine using virus-like particles (VLPs). The VLP vaccine protected macaques from Chikungunya viral infection.

The work was led by Gary J. Nabel of the National Institute of Allergy and Infectious Diseases (Bethesda, MD). VLPs mimic virus particles and stimulate the immune system to produce antibodies, but they are not infectious. Nabel's group immunized rhesus macaques with the VLPs and then exposed them to Chikungunya virus 15 weeks later. All the immunized monkeys resisted viral infection, whereas control monkeys that were not immunized became ill (Nat. Med. published online 28 January 2010; doi:10.1038/nm.2105). Next, the scientists purified serum from the macaques, used it to vaccinate immunodeficient mice and then exposed the mice to Chikungunya virus. Mice that received serum from immunized macaques were completely protected from infection, whereas those that received serum from control monkeys became infected and died.

These results suggest that a VLP vaccine may be able to prevent Chikungunya virus infection in humans. Nabel's group plans to carry out clinical trials to evaluate this possibility.