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 t
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Contact: Sharon Parmet
sparmet@mcis.bsd.uchicago.edu
773-702-6241
University of Chicago Medical Center
3-Aug-1999