Factor for acquiring skin barrier function identified

August 03, 1999

Researchers at the University of Chicago have discovered a critical factor necessary for the skin to acquire its barrier function--the ability to keep water in and microbes out. Their findings, based on knockout mouse studies, provide researchers with an animal model on which to test novel therapies for premature babies whose skin has not acquired barrier function.

Barrier function is acquired in humans during the ninth month of pregnancy. Premature babies born before barrier function is acquired face numerous problems, including weight loss (due to dehydration) and a high risk of infection.

"For the first time we have a mouse model for premature babies with who lack barrier function," says Julie Segre, a post doctoral fellow in the lab of Elaine Fuchs, PhD, Amgen Professor of molecular genetics & cell biology and Howard Hughes Investigator. "This lets us test new therapies and genetic modifications that might restore barrier function as well as see what kinds of side effects these new treatments might have."

In the August issue of Nature Genetics, Segre reports that mice lacking the gene Klf4 never achieve the ability to keep substances from penetrating through their skin. These mice loose weight rapidly after birth due to acute dehydration. Klf4 codes for a transcription factor which binds to specific sites on the DNA strand and turns gene expression on or off.

Genetically engineered mice that lacked the Klf4 gene looked identical to normal mice at birth, but lost weight rapidly and died 12 hours after birth. When Segre immersed these newborn mice in a blue dye solution, they absorbed the dye, turning blue inside and out. The knockout mice never achieved the ability to prevent the dye from entering their bodies, leading the researchers to believe that Klf4 must be a crucial factor for the skin to achieve barrier function.

When Segre looked at the skin of Klf4 knockout mice under the microscope, she found that the granular layer of the skin looked different from that of normal mice.

The skin is continuously regenerating, with new epidermal cells emerging from an underlying proliferative layer and migrating through several upper layers before reaching the skin surface. When underlying cells reach the granular layer, they make a specialized protein coat called the cornified envelope, which acts as a scaffold on which fat molecules assemble to form a sealed barrier. "In the Klf4 knockout mice, the cornified envelope looks immature," Segre says. "Instead of looking round and plump, they are fragile and crumpled."

Additionally, the fat layer, which forms the sealed barrier, was broken in mice lacking Klf4.

"Because the cornified envelope scaffold is malformed, the fat layer doesn't have a smooth surface to bond to. Its like a trying to build a flat highway on a broken surface--it just doesn't work," explains Segre.

The research was funded by the Damen Runyon-Walter Winchell Foundation and the National Institutes of Health.
-end-


University of Chicago Medical Center

Related Premature Babies Articles from Brightsurf:

Historical redlining linked to premature births, lower birth weight babies
Adverse birth outcomes -- including premature births, low birth weight babies and babies who are small for their gestational age -- are more likely to occur in neighborhoods that were once redlined, finds a new study by University of California, Berkeley, researchers.

Traditional vegetable diet lowers the risk of premature babies
It turns out we should follow our parent' advice when we're thinking about becoming parents ourselves, with a study finding eating the traditional 'three-vegies' before pregnancy lowers the risk of a premature birth.

Giving billions of live bacteria to boost the gut health of premature babies
Boosting the milk of premature babies with healthy bacteria may have helped half the number of serious gut problems and infections, according to new research.

Gut microbiome of premature babies is associated with stunted growth
Researchers studied the gut microbiomes of dozens of NICU babies and followed them until they turned age four.

Immune 'control switch' could prevent brain injury in premature babies
About 15 million babies are born prematurely around the world each year and many suffer brain injuries when their immune response goes into overdrive.

New insights into how to protect premature babies from common brain disorder
Premature babies have delicate brain tissue that is prone to bleeding and can result in post-hemorrhagic hydrocephalus, a dangerous condition that leads to excess fluid accumulation and brain dysfunction.

Scientists developing way to help premature babies breathe easier
Researchers suggest a possible cell-based therapy to stimulate lung development in fragile premature infants who suffer from a rare condition called Bronchopulmonary Dysplasia (BPD), which in the most severe cases can lead to lifelong breathing problems and even death.

Music helps to build the brains of very premature babies
In Switzerland, 1% of children are born 'very prematurely.' These children are at high risk of developing neuropsychological disorders.

Specific identification of chronic lung disease in premature babies
Infants born prematurely frequently develop a form of chronic lung disease known as Bronchopulmonary Dysplasia.

Study shows how light therapy might help premature babies avoid vision problems
Scientists discovered a light-dependent molecular pathway that regulates how blood vessels develop in the eye.

Read More: Premature Babies News and Premature Babies 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.