Researchers have generated mouse clones using DNA from neurons in mouse noses. They claim this is the first time living animals have been cloned from cells that have stopped dividing. The study also demonstrates, contrary to what many suspected, that there was no rearrangement of DNA that would have prevented such cells from starting over.
Most clones have originated with DNA from cells that divide often and easily, such as skin cells. This plasticity is thought to make their nuclei more susceptible to being reprogrammed when transferred to an egg. Nerve cells, by contrast, don't reproduce once they reach maturity, says study director Kevin Eggan, now at Harvard.
Taking up this challenge, a team at Rudolf Jaenisch's lab at the Massachusetts Institute of Technology transferred the nuclei of olfactory neurons into egg cells whose nuclei had been removed. Of 352 attempts, 48 developed to the blastocyst stage. The scientists then set up an intermediate stage, creating three embryonic stem cell lines, they report online 15 February in Nature. Using these cells, the scientists were able to obtain more than 40 fertile, cloned mice. According to Eggan, the work shows that, at least theoretically, "any cell type will do as donor."
"This is an impressive study" which "clears up a longstanding scientific question," says Robert Lanza, medical director of Advanced Cell Technology in Worcester, Massachusetts. It's the first time, he says, that scientists have shown that DNA from a fully mature cell "can be forced to reenter the cell cycle. ... There are no irreversible genetic changes to the cell's genome that would prevent it from being reprogrammed."
Indeed, the research eliminates a leading theory of how neurons diversify. Each olfactory neuron codes for only one of a thousand possible receptors that respond to particular sniffed compounds. Scientists have suspected that, like cells in the immune system, olfactory neurons diversify through recombination--that is, each cell randomly shuffles its DNA so it carries a slightly different version of the same gene. If olfactory neurons followed that strategy, says Eggan, the clone would have only one type of olfactory receptor and thus a drastically reduced sense of smell. But it turns out the clones had the full range of olfactory receptors.
Rudolf Jaenisch's lab