Genetic Analysis of the Predisposition to Audiogenic Seizure Fits in Krushinsky-Molodkina Rat Strain

Abstract

The expression of audiogenic seizure fits has been studied in F 1 hybrids between audiogenic seizure-prone Krushinsky-Molodkina rat strain and Wistar rats not prone to audiogenic seizures, as well as in two backcross generations. Only 10% of F 1 hybrids exhibit audiogenic seizure fits, whereas the frequency of this character in two generations of their backcrosses with Krushinsky-Molodkina rats is about 50%. A digenic model with incomplete penetrance has been put forward to explain the control of audiogenic seizure fits. This model fits the data obtained: the theoretically expected distributions of the character in offsprings of different crosses do not differ significantly from those observed in experiments. The model explains why the distribution of the character is the same in the first and second backcross offsprings. GENERAL GENETICS

The Krushinsky-Molodkina rat strain: The study of audiogenic epilepsy for 65 years

“…On the basis of hybrid populations (Wistar × KM F2 and backcrosses), the selection for the experiment regarding the absence of AS started in 1998 [14]. Selection experiment data demonstrated that in the strain selected for the absence of audiogenic seizures in response to sound (strain "0"), the proportion of animals with no AS up to F21 was at the level of 50-60%.…”

“…The study in which the AS intensity and the postictal catalepsy occurrence were analyzed had been performed at the early stage of strain "0" and "4" selection [14]. The tests for spontaneous catalepsy (before sound exposure) showed that this state could be detected in a certain proportion (32%) in KM rats only among the eight rat groups tested.…”

“…A -AS intensity in arbitrary units (ordinate) (grade 4 is the maximal intensity of tonic seizure). B -postictal audiogenic catalepsy, ordinate -the percentage of animals expressing catalepsy: during 1-5-min interval after the end of AS (white columns) and after 10-min interval (black columns) (modified from [14]). …”

Audiogenic Epilepsy -- The Pathological Neural Net and Genetic Predisposition

“…The slow increase in the number of non-prone animals in the "0" strain, as well as the data on diallel cross, using rats of 5 genotypes permit to conclude that the AE proneness in polygenically determined [5]. Another option, as shown by analysis of AE in F2 hybrids KM x Wistar, is that AE is determined by two major genes with several genes-modulators [13].…”

Audiogenic Seizures - Biological Phenomenon and Experimental Model of Human Epilepsies

“…The selection success in first ten selection generations of this selection experiment is demonstrated in fig 2. The percentage of rats, demonstrating "0" reaction (which was verified by sound exposure for 2-3 times with no less than one week intervals) was never very high, being about 40% in average. The more thorough analysis performed at the initial stages of selection demonstrated that the distribution of audiogenic sensitivity in F2 and backcrosses corresponds significantly to the two-gene-incomplete penetrance model (Fedotova et al, 2005). The spontaneous mutation in the rat Wwox gene (Ide/Ide rats) induced dwarfism, postnatal lethality, male hypogonadism, as well as high incidence of epilepsy, typical audiogenic seizures as well, and many structural cell anomalies in the hippocampus and amygdale (Suzuki et al, 2009).…”