Dravet rat model captures seizure disorder’s early features
New version may be more suited for long-term research than other models
Researchers have created a new rat model of Dravet syndrome that captures early features of the disease that may make it more suitable for long-term studies than other models.
The study, “A novel rat model of Dravet syndrome recapitulates clinical hallmarks,” was published in Neurobiology of Disease.
Animal models are crucial for scientific research, providing a platform for understanding the biological underpinnings of diseases and testing treatments. Mice are commonly used for studies and several mouse models of Dravet syndrome have been developed.
Although these mouse models show many characteristic symptoms of Dravet, including heat-induced seizures, the mice have much higher rates than Dravet patients of seizure-related death. As a result, studies with these models are usually limited to very young mice, which makes it impossible to gather long-term preclinical data on potential therapies.
“A valid animal model that facilitates follow-up studies throughout the entire lifespan is therefore urgently needed,” wrote researchers in China who created a Dravet rat model for long-term studies. The researchers noted rats are generally considered a reliable species for studying seizure disorders.
A rat mouse model more similar to people with Dravet
Using genetic engineering techniques, the researchers developed rats that carry one healthy copy of the SCN1A gene and a second mutated copy — mimicking the most common cause of Dravet.
Compared to rats without mutations, the model rats had significantly lower SCN1A gene activity in their brains, as expected. Young model rats all had heat-induced seizures, Dravet’s hallmark symptom, which were completely absent in rats without mutations.
When Dravet rats had the seizures, there was increased activation of nerve cells in the brain regions, the hippocampus and the medial preoptic nucleus, and the patterns of brain electrical activity during seizures were similar to people, tests showed.
Until model rats were subjected to heat to induce a seizure, their brain development and behavior were indistinguishable from rats without Dravet syndrome, the researchers said, noting that’s like what’s observed in babies with Dravet, who usually don’t have any developmental abnormalities until the first seizure. For this reason, the model could be used to study the consequences of early seizure activity in more detail, they said.
Unlike mouse models, the rats don’t appear to die from seizures, which makes them suitable for long-term research, Still, more research is needed to characterize the rat model over the long term and assess its utility for testing therapies, they said.