What is the Frings audiogenic seizure sensitive mouse?

Answer: The Frings mouse develops seizure-like activity upon exposure to certain auditory stimuli, making it an animal model for seizures.

Frings audiogenic seizure sensitive mouse

The Frings mouse was first described in a 1951 publication in the Journal of Mammalogy (Behavior Patterns of the Laboratory Mouse under Auditory Stress). Genetically, some abnormal element in chromosome 13 called the monogenic audiogenic seizure susceptible (MASS1) gene, produces the phenotype observed in these Frings mice. The mouse was named after the researchers who initially characterized the behavior of the mouse.

The Frings mice are used for modeling epileptic activity since they begin seizing upon exposure to audio tones at 10 kilocycles per second (10,000 Hz, or 10 kHz) and 20 kilocycles per second (20,000 Hz, or 20 kHz). For reference, 20 kHz is above the audible range for most adults, while 10 kHz is a high pitch sound, often perceptible by many adults. In these Frings mice, these stimuli produced a predictable response that closely approximated the human seizure. The mice would vigorously and rapidly try to climb up the walls of their home cage, as if trying to escape. The tails would be held very stiff, the eyes open, and the animal would move sporadically and violently.

The Frings mouse is used as a model for making predictions about the action of pharmacological agents in the treatment of seizures and epilepsy. For example, two different anticonvulsant drugs, phenytoin and ethosuximide, are able to block the development of audiogenic seizures in the Frings mice. However, the model does not have high predictive validity, since these drugs are not always effective at treating the human condition.

Studies with the Frings mice

Some studies have looked for neural differences between these Frings mice and control mice. For one, it was found that cellular activity was enhanced (as measured by c fos immunostaining) in the tonotopic region of the inferior colliculus (c-Fos immunohistochemical mapping of the audiogenic seizure network and tonotopic neuronal hyperexcitability in the inferior colliculus of the Frings mouse). This may explain the phenotype of the mouse, since unusual activity at these auditory input areas of the brain may be the factor that contributes to seizure-like activity.

There are also changes in the neurochemical properties of the brains of the Frings mice. First, it was found that the activity of the enzyme tryptophan hydroxylase was decreased compared to control mice. Tryptophan hydroxylase is the enzyme that is responsible for synthesizing serotonin. Despite the changes in the synthetic enzyme, there were no changes in total serotonin levels. Two other neurochemical changes were noted: In the audiogenic seizure sensitive mice, the cerebral cortex had elevated levels of norepinephrine, and the neostriatum had elevated levels of dopamine. (Altered neurochemical parameters in the brains of mice (Frings) susceptible to audiogenic seizures.)

They have also looked at changes in the Frings mouse after frequent seizures in order to model the way a human brain may change after frequent seizures. It was observed that expression of the GluR1 subunit was increased in the lateral shell of the nucleus accumbens after a daily seizure regimen. However, expression of GluR2 or GluR3 were unchanged. (Glutamate receptor GluR1 expression is altered selectively by chronic audiogenic seizures in the Frings mouse brain)