Mangano Lab Creates First Genetic Rat Model of Hydrocephalus
The first-ever genetic rat model of hydrocephalus, created at Cincinnati Children’s, opens up new possibilities to study this neurologic disease. Researchers working with Francesco Mangano, DO, director of the Division of Neurosurgery, used CRISPR/cas9 genome editing technology to generate multiple models of genomic dysfunction related to hydrocephalus.
The process of genetically altering the rats is similar for mice, but few institutions have the technology and capability to manipulate fertilized rat eggs in a highly effective manner. “We collaborated with the Transgenic Animal and Genome Editing Core at Cincinnati Children’s and used CRISPR/Cas9 to introduce the mutation into the embryos,” says June Goto, PhD, an instructor in the Mangano lab. “Then we transplanted the modified embryos into the recipient rat. We were able to generate rat models of hydrocephalus with various genomic dysfunctions, including progressive hydrocephaly (prh), X-linked hydrocephalus (XLH) and XLH with ventriculomegaly.”
Rats can grow to a size of 300 grams or more, while mice typically grow to approximately 30 grams. “These larger rodents allow us to test surgical interventions and non-invasive imaging procedures, something that is not possible with mouse models,” says Mangano. “Our early imaging research using the rat model is yielding data relevant to human hydrocephalus.”
Using a rat model of XLH, the researchers investigated the ability of diffusion tensor imaging (DTI) to quantify white matter alterations resulting from mild ventriculomegaly. “We found that in the rat model, water diffusion tendencies were similar to what is found in humans with the same pathology,” Goto says. “This suggests that the disease process is similar for both rats and humans. While ethical considerations prevent us from obtaining human brain tissue affected by XLH, this finding about white matter alterations suggests that what we learn about the brain tissue of our rat model may help us better understand the disease in humans.”
The research team plans to build on this finding by using DTI before and after shunt surgery to model human congenital hydrocephalus cases. Another potential project involves doing a biochemical analysis of cerebrospinal fluid in the hydrocephalus rat model.
The Mangano lab will present several studies related to the rat model of hydrocephalus at the Pediatric Section of American Association of Neurological Surgeons meeting in Houston in November.
2018 Neurosurgery Conference for Advanced Practice Providers
The Cincinnati Children's Division of Neurosurgery will host its fifth annual Advanced Practice Provider Neurosurgery Conference April 19-20, 2018, at the medical center. The conference will feature presentations by faculty and advanced practice providers, who will share cutting-edge practices within pediatric neurosurgery.
To learn more, contact Allie.Mains@cchmc.org.
