North Carolina State University News Services Campus Box 7504 Raleigh, N.C. 27695 (919) 515-3470
Media Contacts: Dr. W. James Croom, 919/515-8788 or [email protected]
Tim Lucas, News Services, 919/515-3470 or [email protected]
July 1, 1998
Study Yields New Insights on Effect of Down Syndrome on Nutrition
FOR IMMEDIATE RELEASE
Pediatricians and parents have long suspected that children with Down syndrome are more likely to suffer from malnutrition than other kids. But scientists' efforts to investigate this hypothesis have been hindered by the lack of a viable, nonhuman model organism to use in experiments.
Now, a two-year study led by scientists at North Carolina State University has identified a suitable model.
The study, published in the journal Growth, Development and Aging, documents for the first time that the impaired metabolisms of laboratory mice with an extra copy of the 16th chromosome correlate to metabolic defects reported in humans with Down syndrome, who have an extra copy of the 21st chromosome.
"This tells us these mice can serve as an animal model for studying the mechanics of, and potential therapies for, nutritional deficiencies in humans with Down syndrome," says lead researcher Dr. W. James Croom, professor of nutrition and physiology at NC State.
"If you search the literature, there's a lot of anecdotal evidence from doctors and parents, but a paucity of scientific studies," he says. "Because of the differences in metabolism caused by Down syndrome's extra chromosome, it's highly likely these kids' nutrient needs are different and that their ability to absorb nutrients from their food is impaired. Our failure to address these special nutrition needs may compromise their general health."
In their published paper, "Jejunal Function and Plasma Amino Acid Concentrations in the Segmental Trisomic Ts65Dn Mouse," Croom and his colleagues describe the results of their two- year study of nutrient absorption and metabolic energy costs -- the amount of calories burned to absorb food -- in 19 Down syndrome-model mice and 18 control mice.
In vitro tests of intestinal tissue revealed that the Down syndrome-model mice had to expend up to 20 percent more metabolic energy than did the control mice to absorb nutrients from glucose.
"We also found that they had a clear derangement in the way they metabolized protein," Croom says. "All these findings line up very well with the few medical studies that have been done." In vivo tests are now being conducted on mice to corroborate the in vitro findings.
Croom's co-authors on the study are Dr. Ian Taylor, chair of the Department of Medicine at the Medical University of South Carolina; Dr. Eugene Eisen, William Neal Reynolds Professor of animal science at NC State; Dr. Linda Daniels, research analyst in poultry science at NC State; Dr. Evan Jones, retired professor of animal science at NC State; and Joseph Cefalu, a former master's student at NC State, now enrolled in medical school at East Carolina University.
In addition to his ongoing tests on glucose absorption, Croom is conducting further tests on the mice's protein metabolism with Dr. Marcos Fernandez, a Louisiana State University animal scientist. He also is working with Dr. Jerry Spears, an NC State animal scientist, to investigate the mice's absorption of aluminum. "Humans with Down syndrome inevitably develop Alzheimer's disease by their 30s or early 40s. Since recent medical studies have shown a potential link between aluminum absorption and Alzheimer's development, we want to study it in these mice," Croom says.
Croom's studies are supported in part by grants totaling about $60,000 from F.R.I.E.N.D.S. of Trisomy 21 Research Inc. of Los Angeles, a private foundation that sponsors research on issues related to Down syndrome. NC State provides in-kind support for the research. (To learn more about F.R.I.E.N.D.S. of Trisomy 21 Research, or to help support the research it sponsors, write to the foundation at 11718 Barrington Court, #511, Los Angeles, Cal. 90049.)
The Down syndrome-model mice used in the study were developed by Dr. Muriel Davisson at Jackson Labs in Bar Harbor, Maine. They have been used by scientists for years to study how Down syndrome affects neurological functions, but until now no one knew they also could be used to study nutrition and metabolism.
Croom began studying the link between Down's syndrome and metabolism about five years ago. "I was studying livestock nutrition and metabolism at the time, and this was an offshoot of that research. To me, that's always been one of the most satisfying aspects of this study: It shows how agricultural research can have applications in human health, too."
Down syndrome in humans is caused by an extra copy of the 21st chromosome. It's characterized by mental retardation, a weakened immune system, a shortened life expectancy, and distinguishing physical traits that include extra skin folds near the eyes and a short, heavyset body.
-- lucas --
EDITOR'S NOTE: The abstract from Dr. Croom's paper follows. For a copy of the full paper, contact Croom at (919) 515-8788 or Tim Lucas, News Services, at (919) 515-3470.
"Jejunal Function and Plasma Amino Acid Concentrations in the Segmental Trisomic Ts65Dn Mouse"
Published June, 1998, in Growth, Development and Aging, Vol. 62, #1/#2
Authors: J.A. Cefalu, W.J. Croom Jr., E.J. Eisen, E.E. Jones, L.R. Daniel (all of North Carolina State University), and I. L. Taylor, Medical University of South Carolina
ABSTRACT: Mice trisomic for the distal portion of MMU 16 (Ts65Dn) were examined for differences in jejunal function and plasma amino acids as compared to diploid controls. Eighteen control and 19 Ts65Dn mice were compared for whole-body and intestinal O2 consumption, jejunal glucose uptake, and plasma amino acid concentrations. Ts65Dn mice consumed less (p<0.02) O2 per gram of fasted body weight. No significant differences were found in either active or passive glucose uptake. Oxygen consumption by jejunal tissue was not different between Ts65Dn and control mice. The apparent energetic efficiency of jejunal active glucose uptake (nanomoles ATP expended/nanomoles glucose uptake) was significantly higher (115.6 vs. 80.8; p<0.05) in Ts65Dn mice. Histomorphometric analysis of jejunal mucosa showed that Ts65Dn mice had shorter villus height (p<0.04) and decreased planar villus circumference (p=0.05). No differences were found in total jejunal protein (milligrams/grams) or DNA (mill! igrams/grams) concentrations. Significantly higher concentrations of plasma tyrosine, phenylalanine, valine, leucine, isoleucine and citruline (p<0.05) were found in Ts65Dn mice. Lower plasma concentrations of hydroxyproline were detected in Ts65Dn mice (p<0.05). These data suggest that Ts65Dn mice have anomalies in digestive function and amino acid metabolism as compared to normal, diploid controls.
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