Spina Bifida Gene Identified

Australian researchers have identified a gene that causes neural tube disorders (NTDs) in mice, a finding that may lead to genetic testing and new treatments for the conditions in humans.

The NTDs spina bifida and anencephaly are the second most common type of birth defect, affecting 1 in 1,000 births, and are known to have both genetic and environmental components. Women who take in sufficient folate at the time of conception have a substantially reduced risk of delivering a child with a NTD; however, 30% of NTDs seem to be folate-resistant.

The mutant mouse curly tail (ct/ct) has long been used as a model for studying NTDs, although the causative mutation was not known. Now, a group led by Stephen M. Jane of the Royal Melbourne Hospital (Victoria, Australia) report that 100% of mice lacking a functional copy of the gene Grhl3 exhibited a phenotype consistent with severe spina bifida (Nat. Med., December 2003). Chances seem good that this gene, which encodes a developmental transcription factor, will be found to be involved in spina bifida in humans, because the mouse and human genes are virtually identical.

With a Little Help from Their Friends

Everybody knows how helpful the support of a few good friends can be, but a new study in baboons goes a step farther, providing evidence that strong social ties can directly benefit reproductive fitness by enhancing the likelihood of infant survival.

The study, conducted by Joan B. Silk from the University of California at Los Angeles, incorporated data collected from two well-studied groups of wild savannah baboons in Kenya (Science, 14 November 2003). The data indicated a direct positive correlation between the level of socialization exhibited by female baboons, as indicated by the frequency with which subjects were found in close proximity to or engaged in grooming with other females, and the probability of their offspring surviving to one year of age. These apparent benefits of increased social contact remained statistically significant even after the data were adjusted to account for differences in social standing and habitat conditions.

Previous research has identified similar benefits resulting from regular social contact in a variety of nonhuman primate and other mammalian species. Humans also show such beneficial effects, and the authors cite several studies that indicate the positive impact of strong social ties on health and well-being. Although the specific mechanisms behind this increased infant survival remain to be delineated, this study provides new evidence of the important adaptive value of social relationships.

A Shared Switch for Different Drugs

New research has identified a single protein that seems to be involved in the signaling cascades for three different types of psychotropic drug.

d-amphetamine, LSD, and PCP all fall under the generic classification of psychotomimetics—that is, compounds that can induce mental symptoms similar to those seen in schizophrenic patients. These three compounds act specifically on dopaminergic, serotonergic, and glutaminergic neurons, respectively—the same three subtypes of neurons whose dysfunction has been implicated in the etiology of schizophrenia. In an effort to identify a common element for these three pathways, a group led by Paul Greengard from Rockefeller University (New York, NY) examined the potential role played by DARPP-32, a key signaling regulator expressed in all three neuronal subtypes (Science, 21 November 2003).

Transgenic mice lacking expression of DARPP-32 showed an altered response to all three drugs and showed a significant attenuation of the stereotypical behaviors, such as increased repetitive motion, that are observed in similarly treated wild-type mice. Treatment with any of these drugs was also found to trigger the phosphorylation of specific serine and threonine residues on DARPP-32 in the striatum and frontal cortex, regions of the brain that are dysfunctional in schizophrenic patients. By comparison, treatment did not trigger phosphorylation of other unrelated signaling proteins, nor did it affect DARPP-32 phosphorylation in other structures of the brain. By mutating individual serine and threonine residues, Greengard's group was also able to identify the specific amino acids that are involved in mediating the action of DARPP-32 in response to each drug. These combined findings strongly support a model in which DARPP-32 is a shared regulatory component for signaling in response to a variety of psychotomimetic agents.