Study Alters Mice Behavior by Inserting Other Species' Gene

TIMES STAFF WRITER

Mice, natural loners, can be transformed into gregarious social creatures by receiving a gene transplanted from the prairie vole--proof for the first time that switching genes from one species to another can alter behavior, scientists report today.

The research, conducted by scientists at Emory University in Atlanta, eventually could lead to new treatments for behavioral disorders, including schizophrenia, autism and other diseases that are marked by isolation and difficulty in forming personal attachments, the researchers said.

Largely by studying the personalities of twins who were raised separately, scientists have estimated that about one-third to one-half of human social behaviors have genetic origins. But precisely which genes are involved in human behavior remains unclear, with most probably consisting of a large, complex network of interactions.

In this case, only a single gene was involved, with the researchers creating the cuddling vermin by transplanting a gene from a prairie vole, a small, outgoing rodent.

Mice and many other animals, including humans, have their own version of the gene, called the vasopressin receptor.

Though the gene is very similar among the various species, its chosen stomping grounds within the brain vary wildly. In fact, species that look physically identical can be differentiated purely based on vasopressin receptor patterns.

In their study, reported in today's Nature, the Emory researchers inserted vole vasopressin receptor genes into mice and compared their behavior to that of normal mice.

Normal male mice put in a cage with a female briefly would sniff her and then move on to explore the rest of their environment. Mice with the altered pattern of vasopressin would spend significantly more time with the female, said Larry Young, a psychiatry professor at Emory University.

"The [male mice] became much more interested in the female," he said. "They spent more time with her, smelling her, grooming her and generally being nice to her."

Originally, the Emory scientists observed two kinds of voles, prairie and montane, that have 99% identical DNA. Regardless, the social behaviors of the prairie voles and montane voles couldn't have been more different.

Prairie voles, both males and females, are monogamous mates and devoted parents; if put in a large cage, they will spend more than half their time in contact with each other. The montane voles mated promiscuously and soon abandoned their children, and would spend only about 5% of their time interacting with other voles.

One difference, at a genetic level, seemed to center on what part of a male vole's brain interacted with vasopressin.

This difference, the researchers said, is due to a change in the "promoter" for the vasopressin receptor, a part of a gene that seems to determine where and when the gene is expressed.

To prove that receptor location was important in determining behavior, scientists turned to mice, whose genes are relatively easy to manipulate. By putting a prairie vole promoter into the mouse vasopressin receptor, the researchers affected a prairie vole-like distribution of receptors, and the related behavioral shift.

Vasopressin is a hormone that had already been implicated in "male typical behavior" in a number of species. These behaviors span a wide range, from hamsters' aggression toward other males to the song of some male birds to prairie voles' doting parental skills.

Previous work also had implicated oxytocin--a chemical relative of vasopressin found more abundantly in females--in autism. A study of 30 autistic boys showed that they had only half the oxytocin of their average peers. Even among non-autistic children, a high degree of social smoothness appeared to correlate with a relatively high oxytocin level.

Young's findings certainly will spur more interest in a possible similar role for vasopressin, according to scientists who study the interaction of behavior and genetics. Other diseases that result in feelings of isolation and social detachment, including Tourette's syndrome, schizophrenia and Alzheimer's disease, may exhibit vasopressin irregularities, Young and his colleagues said.

Oberlin College psychology professor Norman Henderson, editor of the journal Behavior Genetics, finds the prospect interesting.

"There are certain behaviors that are going on in psychotic [diseases] that could possibly be related to this receptor," he said.

It is too soon to say whether your significant other's cuddle quotient is affected by the neural distribution of vasopressin receptors, however.

According to Henderson, it is unlikely that vasopressin works alone to mold such complex behavior as human social interaction. Instead, he said, humans are likely to have a number of "modifiers" for a given trait: genes that either pump up the effect of another gene or damp it down.

And even if the entire network of behavior genes and modifiers in humans is investigated and eventually spelled out, it seems doubtful that claiming "my genes made me do it" to explain away infidelity will ever be considered very convincing.

As researchers point out, humans should be able to tell the difference between a biological instinct and a biological imperative.

"We [humans] inhibit our behaviors a lot," Henderson said. "Our brain tells us not to behave in certain ways, even if there is some instinct to."

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