Jefferson Scientists Use Gene Repair Technique To Change Albino Mice Cells To Black

November 29, 1998

Researchers at Jefferson Medical College have used an innovative 'gene repair' technique in the laboratory to genetically change white albino mice color-producing cells to black. Not only have the cells turned black, but the scientists showed for the first time that such changes are both permanent and can be passed to offspring.

The work holds promise as a potential treatment for some hereditary diseases by correcting the genetic mutation from which they arise.

Kyonggeun Yoon, Ph.D., associate professor of dermatology and cutaneous biology and biochemistry and molecular pharmacology in Jefferson Medical College at Thomas Jefferson University in Philadelphia and postdoctoral fellow Vitali Alexeev, Ph.D., corrected a single alteration in the gene that controls skin color in albino mice cells. The alteration, known as a 'point mutation,' was in the gene for a key enzyme, tyrosinase. Tyrosinase is involved in making melanin and in pigmentation. By correcting the alteration, tyrosinase activity was restored and melanin was again produced, changing the color of the cells.

The researchers' work appears Nov. 30 in the journal Nature Biotechnology.

"Melanin-producing cells become normal, changing albino to black," says Dr. Yoon, who is also a member of the Jefferson Institute of Molecular Medicine. "Once the mutation is corrected, it takes five or six days for the entire biochemical process to begin producing melanin."

Dr. Yoon explains that she used the technique on melanin-producing cells as a model system to test a hypothesis. "We wanted to see what we could visualize and follow using this system," she says. "We can clone the black cells, and using a process called clonal analysis, show that this gene has been corrected and stable. Showing the change in the gene, protein level and color hasn't been done before."

Dr. Yoon and colleague Eric Kmiec, Ph.D., associate professor of microbiology and immunology at Jefferson Medical College and a member of Jefferson's Kimmel Cancer Center, developed the gene-fixing technique several years ago. Scientists can synthesize a small oligonucleotide--DNA interspersed with small amounts of RNA--that has the capability to find and attach itself to a certain part of a gene. The small genetic vehicle is designed to trigger the cell's normal DNA repair system into action as well. The repair mechanism scans the DNA looking for any mismatches or two strands of DNA that don't seem in sync. When it finds a mismatch, it replaces one of the chemical bases with one that fits better. The scientists, then, can use this natural repair system to correct a bad mutation.

The gene-repair technique is far from perfected, Dr. Yoon says. "Much more research is needed to improve the design and make this technology generally applicable. Skin is an ideal organ on which to test this technology since it is accessible and can be monitored."

Thomas Jefferson University

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