Jefferson Researchers First To Create Genetically Engineered Mouse To Study Photoaging

February 17, 1998

Embargoed until Tuesday, February 17, 1998 at 12:30 p.m. EST. Dr. Jouni Uitto will present study results at the 1998 American Association for the Advancement of Science (AAAS) annual meeting at the Pennsylvania Convention Center, Philadelphia, Pa.

Jefferson Researchers First to Create Genetically Engineered Mouse to Study Photoaging Transgenic mouse leading to better understanding of how ultraviolet light exposure contributes to skin aging and skin cancer and the development of new, better sunscreens that may prevent both.

Researchers from Jefferson Medical College of Thomas Jefferson University, Philadelphia, have developed the first transgenic, or genetically altered, mouse used to study the causes and effects of photoaging on human skin. The mouse line, developed by microinjecting fertilized mouse eggs with human elastin promoter DNA, the material which produces skin fibers that promote elasticity, has enabled Jefferson researchers to learn more about how the ultraviolet light rays UVA and UVB cause skin aging and wrinkling.

Study results have also led to new ideas for how sunscreen formulations and other compounds may be designed to block the skin from the dangers of UVB, which many already do, and UVA, which causes skin aging and may play a role in skin cancer but is not blocked as well by traditional sunscreens. These findings will be presented by Jouni Uitto, M.D., Ph.D., professor and chairman of the department of dermatology and cutaneous biology at Jefferson Medical College of Thomas Jefferson University, at the 1998 American Association for the Advancement of Science (AAAS) annual meeting in Philadelphia, on Tuesday, February 17.

Dr. Uitto's presentation, "Molecular Assays for Solar Effects in Skin," will serve as part of a larger seminar, "Sunscreen and Skin Cancer: What's Happening," proposed and organized by Francis Gasparro, Ph.D., research professor in Jefferson?s department of dermatology and cutaneous biology.

Dr. Gasparro, an expert in photobiology, and author of the newly released book, Sunscreen Photobiology: Molecular, Cellular and Physiological Aspects, recognizes the new transgenic mouse line as one step in understanding that most sunscreens currently on the market are not completely protecting consumers' skin from sun damage.

"There is currently more sun exposure, skin cancer and, ironically, more sunscreen use than ever before," said Dr. Gasparro. "Sunscreens on the market certainly protect the skin from sunburn by absorbing UVB rays, but other forms of ultraviolet light like UVA, that can also contribute to skin aging and skin cancer, are not completely or only partially blocked by sunscreen. New vehicles for studying photoaging, like the transgenic mouse, can only lead us in the direction of more protective sunscreens."

In photoaged skin, the arrangement of normal elastin fibers is altered and transformed into large haphazard clumps, causing the skin's exterior to become leathery and wrinkled. Dr. Uitto developed and bred the transgenic mice. They microinjected fertilized mouse eggs with human elastin promoter linked to a chloramphenicol acetyltransferase (CAT) reporter gene, which indicates the rate of elastin promoter activation, or photodamage, triggered by exposure to ultraviolet light rays. Eric Bernstein, M.D., associate professor of dermatology and cutaneous biology at Jefferson, developed the use of the innovative transgenic mice as a model of photoaging.

"We wanted to develop a more rapid and sensitive means of studying photoaging and compounds that might protect against sun damage in living tissue," explained Dr. Uitto. "When we exposed the mice to controlled solar simulating irradiation in the lab we learned from the CAT reporter gene that the light acts as a switch, resulting in up to a 30-fold increase in elastin promoter activity indicating photodamage."

Drs. Uitto and Bernstein were able to detect this increase in elastin as early as 24 to 48 hours after irradiating the mice. "Our transgenic mouse is a huge advance because of the rapidity and sensitivity with which we are able to measure results," said Dr. Bernstein. "Other mouse models have taken at least six months to a year to show effects of photodamage caused by irradiation."

The researchers were also able to apply sunscreens and related compounds to the skin of the mice and found a correlative relationship between the sun protection factor (SPF) and the degree to which elastin promoter activity was reduced. "The higher the SPF we applied to the skin of the mice, the lower the percentage of elastin promoter activity, or photodamage, that we measured,? explained Dr. Uitto. ?We saw the highest reduction in photodamage when we applied compounds that protected against UVB and UVA rays."

"The transgenic model adds a molecular component to the evaluation of sunscreen efficacy," added Dr. Gasparro. "Prior to this look at molecular assay, efficacy was based solely on physiological responses. Molecular assays are important because they can provide information about the possible fate of a cell."

The transgenic mice do not have any physical differences that would visually distinguish them from other mice, and they can be bred since they pass along the human elastin promoter linked to the CAT gene to their young. Cell cultures can also be made from tissue biopsies of their skin, which has allowed the researchers to examine the molecular changes caused by photodamage.

"This model has given us a clearer picture of what happens to skin when exposed to different forms of ultraviolet light," said Dr. Bernstein. "Our research has piqued the interest of sunscreen developers who are creating new formulations that protect against UVB and UVA radiation, as well as those interested in free-radical scavengers, which are compounds, specifically Vitamin C and Vitamin E, that protect against chronic skin inflammation resulting from sun exposure. This can only benefit all of us who like to go out in the sun but do not like the wrinkles and aging that the exposure can cause."
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Thomas Jefferson University

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