The study appears in the October issue of the journal of Molecular Endocrinology.
In the U.S., 1,000 to 2,000 children are born with anencephaly each year. Most do not survive more than a day or two. Although anencephaly can sometimes be diagnosed through ultrasound, which picks up the malformation of the head, there is no genetic test, and its cause is unknown.
By breeding special "knockout" mice that were missing the gene for the enzyme called HSD17b7, UIC researchers found that such mice died on the tenth day of gestation with the severe lack of brain development that characterizes the human birth defect.
The failure of the mice to develop, as well as the extreme nature of the changes in the formation of the animals, was very surprising, said Geula Gibori, UIC distinguished professor of physiology and biophysics and principal investigator of the study. Mice that lack enzymes of similar function are born with subtle changes in their cognitive ability, but they survive.
The UIC researchers had previously discovered this novel enzyme and were focused on its role in converting the weak hormone estrogen into the more potent estradiol in the ovaries and its possible role in breast cancer.
Recent research has shown that the HSD17b7 enzyme has an additional role in the last steps of cholesterol biosynthesis. But because the fetus receives cholesterol from the mother during gestation, Gibori and her colleagues did not expect the enzyme to be of much importance to development, she said.
However, it appears that as the fetal mouse brain develops it forms a blood barrier, blocking maternal cholesterol from brain cells. The brain becomes dependent on the biosynthesis of its own cholesterol once this blood-brain barrier forms, at day 10 of gestation.
The UIC researchers established that in the fetus, the brain is the most important site for HSD17b7 expression and provided evidence that anencephaly may result from the loss of this enzyme.
"Creating a knockout mouse is a very laborious process," said Aurora Shehu, first author of the paper and at that time a graduate student in Gibori's laboratory. Mice with only one copy of the gene are produced and then interbred; one in four of their offspring should have no copy of the gene -- a "null" mouse.
"We expected null mice to be born and to be infertile, however, no null mice were born," said Shehu. "I was afraid I had made a mistake, and went back to the beginning, repeating the entire process, but still no null mice were born."
Shehu then began more painstaking work, performing in-utero genetic testing on entire litters -- often 10 to 12 fetuses per litter. She found that the null mice were there, but they were dying at day 10 of gestation, when the blood-brain barrier develops.
Gibori says the gene that is missing or defective in human anencephaly is not yet known, but the discovery that the deletion of HSD17b7 in the mouse causes anencephaly suggests this gene may be awry in the human disease.
"This opens up very exciting possibilities for understanding human anencephaly, and, perhaps, someday being able to provide a genetic test for the condition early in pregnancy -- and ultimately a therapy," she said.
As their next step, Gibori's lab plans to test human anencephalic tissue for a mutation in the HSD17b7 gene.
The study was supported by grants from the National Institutes of Health. Jifang Mao, Gil B. Gibori, Julia Halperin, Jamie Le, Y. Sangeeta Devi and Bradley Merrill of the UIC College of Medicine and Hiroaki Kiyokawa of Northwestern University also contributed to the study.
Jeanne Galatzer-Levy | Newswise Science News
Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology