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Research Roundup

May 8, 2012, Volume 58, No. 33

Identifying a Gene Responsible for Male Infertility and a Respiratory Disorder

A team of researchers from the University of Pennsylvania School of Veterinary Medicine has characterized a protein responsible for sperm tail formation that, when missing, causes male infertility, brain abnormalities and other problems in mice.

Dr. Jeremy Wang, an associate professor of developmental biology and director of the Center for Animal Transgenesis and Germ Cell Research at Penn Vet, led the study, collaborating with postdoctoral researcher Jian Zhou and research specialists Fang Yang and Adrian Leu.

The work, published in the journal PLoS Genetics, has implications for providing genetic counseling and in vitro fertilization to men with certain infertility problems, as well as the one in 16,000 people who suffer from a condition known as Kartagener syndrome, or primary ciliary dyskinesia (PCD).

Some men with infertility have sperm that cannot swim properly. One of the causes of this immobility may be a disruption in the function of cilia, hair-like structures that helps cells move themselves or other objects around. The root cause of PCD also appears to be a defect in cilia function.

Delving into the complex structure of cilia, the Penn researchers examined a protein called MNS1 or meiosis-specific nuclear structural protein 1, which they found located in the sperm tail.

To get at the function of MNS1, the team created mice bred to lack the protein. Though the mutant mice grew normally, fewer were born than expected, indicating that the mutation might be lethal in some embryos or very young mice.

In addition, Dr. Wang said, “the mutation has a very interesting phenotype.”

Male mice that lacked MNS1 were sterile. Their sperm count was only eight percent of that seen in normal mice, and the vast majority of sperm present had very short tails, impairing their ability to swim. The fact that the sperm had normal heads but malformed tails also indicated to the scientist that the MNS1 mutation affected formation of the sperm tail, which is a specialized type of cilium.

In working with the mutant mice, the researchers noticed that more than half bore another unusual trait: some or all of their internal organs were reversed in position, the heart on the right instead of the left and so on. This condition, known medically as situs inversus, is also seen in about half of PCD patients. The patterning and formation of internal organs is another process that is dependent in part on cilia.

With growing evidence that MNS1 played a role in cilia function, the researchers looked to other parts of the body where cilia are vital, including the brain, where cilia direct cerebrospinal fluid, and the trachea, where cilia help move fluid and mucous.

They found that the mutant mice developed hydrocephalus, or a swelled head, consistent with a lack of cilia function. And upon examining cilia in the trachea, they found abnormalities. In the MNS1-deficient mice, the cilia had only about half the normal number of dynein arms, structures that provide the power for cilia to move.
Dr. Wang and colleagues are now working to determine the mechanism by which MNS1 affects cilia function.

“We still don’t really understand how this protein works,” Dr. Wang said. “We’re trying to characterize a number of proteins that potentially interact with MNS1.”
They’re also planning to partner with in vitro fertilization clinics to screen infertile males for deficiencies in the MNS1 gene. If it turns out that some of these men have a mutation that renders MNS1 nonfunctional, Dr. Wang said, “they won’t be able to conceive naturally, but, in the clinic, technicians can just inject the sperm head into the egg and achieve fertilization.”

In addition, if scientists confirm that mutations in MNS1 are responsible for some of the effects of PCD, in the future the syndrome could potentially be treated with gene therapy, which has shown promise in ameliorating certain respiratory conditions.


Mothers of Kids with Autism Earn Significantly Less

Autism spectrum disorders (ASD) are a lifelong set of developmental disorders that often demand significant resources of time and money from families. New research from the Perelman School of Medicine at the University of Pennsylvania and the Center for Autism Research at the Children’s Hospital of Philadelphia (CHOP) now reveals that a wide range of negative parental employment and earnings outcomes are associated with childhood ASD, and specifically have a major impact on a mother’s ability to contribute to the overall income of the family. The new research is published online, in Pediatrics, the official journal of the American Academy of Pediatrics.

“Our results suggest a significant economic burden for families of children with ASD, especially for mothers,” said Dr. Zuleyha Cidav, a postdoctoral fellow at the Center for Mental Health Policy & Services Research at Penn and lead author of the study. “Mothers are often the primary caregiver and decision maker, and therefore have to devote considerable personal resources to obtaining health care services for their children; it is not surprising that, because of these additional responsibilities, these women are less likely to work, work fewer hours per week, and earn substantially less than mothers of children with no health limitation.”

In the study, researchers tracked employment outcomes of parents of children with ASD in order to estimate the average annual loss of parental earnings associated with raising a child with autism in the United States. They broke their sample into three groups: families with children with diagnosed ASD; families with children who did not have diagnosed ASD, but had another health limitation; and families with children with no reported ASD or other health limitations.

On average, mothers of children with ASD earned 35 percent less than the mothers of children with another health limitation, and 56 percent less than mothers of children with no health limitation. They are 6 percent less likely to be employed, and work an average of 7 hours less per week than mothers of children with no health limitation. Fathers’ employment was not impacted. On average, family earnings of children with ASD are 21 percent less than those of children with another health limitation and 28 percent less than those of children with no health limitation.

The authors noted that in the sample, mothers of children with ASD were significantly more educated and older (a proxy for more work experience) than the other two groups. Given the positive coefficients for education and age, the findings suggest that mothers of children with ASD, who potentially could earn more because of their higher educational level and age advantage, actually earn less as a result of the burden of caring for their children with ASD.

“This study shifts perspective in research on the costs of childhood ASD away from system-level health care costs toward family costs,” said Dr. David Mandell, senior study author and associate director of both the Center for Mental Health Policy & Services at Penn and the Center for Autism Research at CHOP. “Parents of children with ASD lack appropriate community-based services and resources needed to support work and family obligations. In ongoing policy discussions regarding the best ways to support families and finance care for children with ASD, it is essential to design universal health care and workplace policies that recognize the full impact of autism on families.”


Food Stamps and Farmers' Markets

Current food stamp programs at urban farmers’ markets attempting to bring fresh produce to economically stressed city dwellers are so complicated for the shopper and expensive for the farmer that fewer people are taking advantage of the federal program designed to help them, according to research at Penn Nursing.

Record numbers of Americans are receiving Supplemental Nutrition Assistance Program (SNAP) benefits, as food stamps are now known, and many SNAP participants live in neighborhoods with little or no access to healthy food. A study conducted at the Clark Park Farmers’ Market in University City found that making it easier for vendors to collect SNAP payments with electronic point-of-sale systems increased fresh produce sales to SNAP recipients by 38 percent.

However, the costs associated with such systems may put them out of reach for farmers. The study, by Penn Nursing Professor Alison M. Buttenheim, and colleagues, appears in the Journal of the Academy of Nutrition and Dietetics. “Our study highlights the need for an equitable approach to subsidizing Electronic Benefits Transfer (EBT) fees at farmers’ markets,” Dr. Buttenheim reported. “Vendors told us, and we confirmed with a cost-benefit analysis, that they would not be able to break even on sales after paying the associated costs.”

SNAP participants access their benefits through EBT cards. To accept the cards at farmers’ markets, vendors must rent wireless POS terminals, pay for wireless service, and cover transaction fees. Because of the associated costs, many market managers operate a single wireless POS terminal for the entire market. SNAP beneficiaries may buy a token that they can exchange for produce, but they can’t receive change. Alternatively, customers can make their selections with a vendor, get a paper receipt for the total amount of the purchase, and present the receipt to the central terminal, where the customer’s EBT card is swiped for the exact amount of purchase. This must be repeated for each vendor the customer wants to visit.

Instead, Dr. Buttenheim and colleagues provided each vendor at the Clark Park Farmers’ Market with a wireless POS terminal for EBT and credit/debit card transactions. A grant covered all associated wireless charges, transaction fees, and processing fees during a pilot program which ran from June 2008 through February 2009. After the pilot period, the market returned to a single market-operated terminal and receipt system.

Researchers analyzed sales data at the market for four years, beginning 17 months before the pilot project and ending 22 months afterward. There was a 38 percent increase in SNAP/EBT sales during the months with multiple vendor-operated terminals. However, after the pilot project ended, sales to SNAP participants returned to pre-pilot levels, controlling for increases in SNAP participation in Philadelphia.

“Many stakeholders want to increase SNAP redemptions at farmers’ markets,” said Dr. Buttenheim. “We hope this study can inform policymakers about the specific mechanisms driving SNAP redemptions and about the need for subsidies for wireless POS technology at farmers’ markets.”

In a podcast, Dr. Buttenheim and co-author Allison Karpyn of The Food Trust, a Philadelphia nonprofit, discuss the impact of wireless POS terminals at farmers’ markets on sales to SNAP beneficiaries, and the policy implications of their research. The podcast is at http://andjrnl.org/content/podcast


Almanac - May 8, 2012, Volume 58, No. 33