Jelly-fish genes help create MAFIA Mice

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    By Lindsay Lansing

    During abdominal surgery, a person”s white blood cells rush to the “injured” area: the incisions. During the intense pain and adhesions that sometimes develop following surgery, the white cells have been blamed.

    However, BYU professor Sandra Burnett has discovered that white blood cells, also known as macrophages, are not to blame.

    With a jellyfish gene and other special proteins, Burnett created a DNA strand, which she injected into mice, to observe the effects of “macrophages” or white blood cells within an animal.

    For many years, these cells were thought to be the source of pain among patients who underwent abdominal surgery. Operations such as gallbladder removal, appendectomy or any other abdominal incision cause patients to develop adhesions, or tissues that bind organs together.

    Adhesions are reported to be the number one reason why people go back in for a second surgery and in 1994, $1.3 billion were spent in treating this problem. According to a press release, they account for 300,000 hospitalizations a year.

    Little did Burnett know when she started her research that her work with jellyfish and mice would be so relevant to clinical research.

    “I first didn”t know what adhesions were, and I had to ask someone to tell me what I was looking at,” said Burnett. “It was exciting to learn that what I was studying had application to such a serious problem in surgery.”

    Burnett”s experiment was focused on the activity and relevance of these macrophages within the body.

    “Prior to Sandra starting in the lab, there was no way to produce a mouse in which there were no macrophages,” said Alan Kaplan, co-chair of the microbiology, immunology and molecular genetics at the University of Kentucky, and who also oversaw Burnett”s work.

    “Many were saying that you could never develop a mouse without macrophages. If you did, the baby itself could never develop,” Burnett said. “So lots of people were saying that you can”t make it. It”s not possible.”

    With this scientific perplexity, Burnett accepted the challenge and worked to create and develop these special mice.

    “We had to come up with an approach to have these mice keep their macrophages during their development, and that at some point during their life, we could give the mouse something to destroy all their macrophages,” Kaplan said.

    And that is exactly what Sandra did. She created a transgene, using florescent proteins from jellyfish and other proteins from around the world to assemble a DNA sequence that she injected into these mice.

    “The gene was segmented together piece by piece and inserted into the egg of that mouse,” Burnett said. “The gene was integrated with the mouse DNA. The mice are then born and the only thing that looks different is that their cells are florescent green.”

    After these rodents have developed, they are injected with a harmless drug, which “makes the macrophages commit suicide,” said Don Cohen, co-chair of microbiology, immunology and molecular genetics at the University of Kentucky. “You treat the animal after its development to activate a gene which eliminates these cells in the mice.”

    MAFIA mice, which stands for Macrophage Fas-Induced Apoptosis, are then created, and their behaviors observed.

    Kaplan said creating the animal was a very difficult challenge. Once this process was complete, the scientists were able to observe the effects of macrophages on the organs and their connection with abdominal irritation and adhesions.

    “The adhesions are what is painful and that causes intestinal obstructions and fertility problems,” Burnett said. “The macrophages were thought to contribute to the problem. They thought they were bad and that we should get rid of them because it”s harder to heal. The concern was that these cells were coming in and hurting instead of helping.”

    Her findings actually proved that macrophages are good and that they can help heal and prevent adhesions from forming and that “there has to be some type of irritation for the adhesions to form. If you have a stitch, it can be irritating enough that the adhesions will form spontaneously,” Burnett said.

    With the creation of these mice, they have been distributed to 30 labs all over the country.

    “We breed them all the time and ship them out as people contact us,” Cohen said. “The generation of this project would not have been possible without Sandra in the lab. Now that she has taken the project to Utah, it is nice to see her expanding it there.”

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