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Mice bred without fosB gene are poor mothers, study pTC shows Mutants allowed infants to die from neglect


Mutant mice that ignore their own infants, allowing them to die from neglect, provide new evidence that in mammals the very essence of mothering -- the ability to nurture the young -- has an important genetic component.

The inattentive mother mice, described in today's issue of the journal Cell, were bred by researchers at the Harvard Medical School to lack a gene known as fosB.

The researchers did not set out to study nurturing; rather, they were curious about fosB, because it is one of many "immediate early genes," which are thought to be crucial players in learning, memory and other types of behavioral change. Such genes react quickly to a wide variety of changes in the environment, and may bring about lasting adaptations in the circuitry of the brain.

"This paper is a very important addition to what we know about these genes, which are involved in a variety of instinctive and cognitive processes," said Dr. Eric Kandel, a professor of neurobiology at Columbia University's College of Physicians and Surgeons, and a senior investigator at the Howard Hughes Medical Institute.

But Kandel cautioned against using the findings to jump to conclusions about human behavior.

"One shouldn't think that this gene is the only way to produce this effect," he said, emphasizing that in higher mammals, and particularly in people, social conditions, experience and other environmental factors, as well as additional genes, will all likely be found to influence complex behaviors like nurturing.

Until now, scientists did not know precisely what fosB did. The Harvard team, led by Dr. Michael Greenberg of Children's Hospital in Boston, created a "knockout" mouse -- a strain of animals lacking fosB -- in the hopes that defects would provide clues about the function of the missing gene.

Initially, the researchers were puzzled by their findings. Despite the lack of fosB, the first generation of mutant mice seemed normal. But when they mated and gave birth, their litters died within a day or two.

Jennifer Brown, a graduate student who conducted the experiments, noticed that the mothers behaved oddly. Unlike normal mice, which gather their pups together in the nest and crouch over them to nurse them and keep them warm, the mutants left their newborns scattered and ignored them. The babies, unfed, untended and probably cold, could not survive.

Subsequent studies showed that the mothers were physically capable of nursing and that later offspring were healthy at birth; removed from the mothers and raised by normal females, the pups thrived. The only possible explanation for the deaths lay in the mutant mothers' failure to take care of their young.

"One of the most exciting things about the knockout approach and our example of it," Brown said, "is that it gives us proof that a particular gene is critical for a particular function."

Pub Date: 7/26/96

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