hydrocephalus in mice genetic malfunction

Genetic Malfunction in Mice Linked to Hydrocephalus

One of every 770 babies in the United States is born with hydrocephalus, a neurological condition for which scientists are still trying to determine the cause and find a cure.

A study conducted at Case Western Reserve University looked at how the removal of a particular gene in mice was linked to hydrocephalus. At Advanced Neurosurgery Associates, a leading neurosurgery practice in New Jersey, we took an interest in the study because of our frequent treatment of patients with hydrocephalus.

Hydrocephalus is a condition in which patients experience an excessive amount of fluid in the brain. Though the name implies that this fluid is water, it is actually cerebrospinal fluid (CSF).

The role of cerebrospinal fluid is to surround and protect the brain and spinal cord. In patients with hydrocephalus, the abundance of CSF results in widening the spaces in the brain known as ventricles. This creates pressure on other areas of the brain.

There are two kinds of hydrocephalus, congenital, with which patients are born and which is thought to be caused by genetic abnormalities, or acquired, which patients develop at birth or later in life from an injury or other disease. This study is especially relevant for those with congenital hydrocephalus because it mainly focused on the genetic component.

Professor Anthony Wynshaw-Boris, MD, PhD, conducted the study, published online in the journal Neuron on July 17th. Researchers looked at how malfunctioning Dishevelleds (Dvl) genes can trigger hydrocephalus in mice. The role of these genes is to regulate the placement and alignment of cilia within ependymal cells found in the ventricles of the brain. Cilia are hair-like protrusions that line the surfaces of cells and move back and forth to promote the motion of CSF.

When the Dvl genes were removed from the mice, the cilia were disorganized and positioned incorrectly, disrupting the smooth flow. One set of mice was completely Dvl deficient from birth, and had normal brain development until adulthood, at which time they developed hydrocephalus. Another set of mice had the Dvl deficiency induced in adulthood, and they experienced an onset of hydrocephalus, with the cilia abandoning their previously normal functioning.

The issue with the cilia lies in their polarity and movement. Without the presence of Dvl, the cilia point in the wrong direction and do not move the CSF effectively. The question now is what this information means for the future of hydrocephalus research. More studies need to be conducted to determine if these results are helpful for humans with hydrocephalus. Determining how genetic components function in mice is an important starting point, but does not necessarily mean that human genetics function in the same way.

Dr. Wynshaw-Boris understands this and says, “Identifying a new cause for hydrocephalus in an animal model will stimulate further scientific investigation to learn if this planar cell polarity pathway is involved in human hydrocephalus.”

While the genetic research is interesting and brings hydrocephalus to the scientific forefront, continued research is needed before the takeaways from this experiment have further applications. In addition, even if the results can be applied to humans, it still needs to be determined how the function of these genes can be altered in human patients with hydrocephalus.