Human Interest

Seoul National University

Ruppy the Fluorescent Puppy Is World's First Transgenic Dog

July 11, 2009 10:00 AM
by Liz Colville
Ruppy (short for Ruby Puppy) is a cloned beagle from South Korea who glows red under ultraviolet light. He's an example of how dogs may be used to study human diseases.

Ruppy's Fluorescence Comes From Gene of Sea Anemone

Ruppy is one of four fluorescent beagle puppies created by a South Korean team led by Byeong-Chun Lee, who worked on Snuppy, the first cloned dog, in 2005. The puppies were created by "cloning fibroblast cells that express a red fluorescent gene produced by sea anemones," reports New Scientist.

A transgenic animal is an animal "in which there has been a deliberate modification of its genome, the genetic makeup of an organism responsible for inherited characteristics," according to the Federation of European Laboratory Animal Associations. The first transgenic animal was a mouse, reports, a nonprofit organization that promotes bioscience education.
The puppies are considered a "proof-of-principal experiment" that "should open the door for transgenic dog models of human disease," according to CheMyong Ko, who worked on the project.

"[D]ue to the technical difficulty in obtaining fertilizable eggs and the unavailability of embryonic stem cells, no transgenic dog has been generated" until now, the authors of the project wrote in an abstract of their findings in the journal Genesis.

The team created the puppies by "first infecting dog fibroblast cells with a virus that inserted the fluorescent gene into a cell's nucleus," New Scientist reported. "They then transferred the fibroblast's nucleus to another dog's egg cell, with its nucleus removed. After a few hours dividing in a Petri dish, researchers implanted the cloned embryo into a surrogate mother."

Background: The first cloned dog

Scientists at Seoul National University successfully cloned the first dog, Snuppy the Afghan, in August 2005. Many were wary of ethical consequences. Animal rights activists accurately predicted what it meant for the future: attracting "pet owners keen to re-create their much loved pets," Dr. Freda Scott-Park, president-elect of the British Veterinary Association, told the BBC.

The process was difficult and preceded by a host of failed attempts; dogs are especially difficult to clone. The second puppy in the experiment died soon after birth. The university stated that since dogs and humans share certain diseases, the clones “could be very valuable in finding technologies useful for curing human diseases.” Public response was tentative and wary.

Opinion & Analysis: Dog transgenesis and cloning

Stanford University geneticist Greg Barsh said to New Scientist the Ruppy project is "an important accomplishment," but Cornell University's Nathan Sutter disagreed, saying "transgenesis is laborious, expensive and slow." The magazine added that because of the team's method, which "used a retrovirus to transfer the fluorescent gene," they "could not control where the virus inserted the gene."

This could mean that in the future, creating a "knockout" dog, the way researchers do with mice and rats, would be a challenge, as would "engineering dogs that produce mutant forms of a gene." "Knockout" animals are engineered to lack a specific gene through a Nobel prize-winning method called gene targeting.

Dr. Gerald Schatten of the University of Pittsburgh School of Medicine, a member of the team that cloned Snuppy in 2005, dismissed that project's relationship to the cloning of pets. "The overall objective of this programme is to learn about the root causes of diseases," he told the BBC at the time. "We believe it is possible, if you can responsibly develop the ability to derive stem cells from cloned dog embryos, that our very best friends may turn out to be the first beneficiaries of stem cell medicine."

But RNL Bio, the South Korean firm responsible for the first cloned dog, Snuppy, created two beagle clones of its own in January "using stem cells derived from fat tissue," Reuters reported. The company said it would hope such an innovation could make cloning a pet dog "easier and perhaps as much as 50 percent less costly."

Related Topic: Cloned pet pitbull becomes commercial first; Dolly the sheep is first cloned mammal

In 2008, Korean scientist Lee Byeong-chun of RNL Bio took frozen cells from a diseased American dog, Booger, and implanted them in surrogate mothers, producing five Booger puppy clones. It was RNL Bio's first venture into worldwide cloning services, the company announced. Owner Bernann McKinney’s relationship with Booger made her feel that he was “more than just a canine companion.” The company hopes to begin a business of cloning 300 dogs a year. 
Scientists first cloned a mammal, Dolly the sheep, in 1997. The response was first and foremost unease and surprise. Charles Krauthammer noted in Time magazine that many people would be thinking Frankenstein-esque thoughts. He predicted that fear, and even laws, would do nothing to stop the advance of cloning, arguing, “You can outlaw technique; you cannot repeal biology.”

Most Recent Beyond The Headlines