1022-7954/05/4111- © 2005 Pleiades Publishing, Inc.
Russian Journal of Genetics, Vol. 41, No. 11, 2005, pp. 1223–1229. Translated from Genetika, Vol. 41, No. 11, 2005, pp. 1487–1494.
Original Russian Text Copyright © 2005 by Fedotova, Kostyna, Poletaeva, Kolpakov, Barykina, Axenovich.
Audiogenic seizure ﬁts develop in response to a
loud sound. A ﬁt consists of the phases of motor excita-
tion, clonic seizures of the extremities and the body,
and tonic extension of the entire body musculature.
This type of seizure ﬁts is classiﬁed as reﬂex epilepsy
and is observed almost exclusively in rodents ,
including laboratory animals (mice and rats).
No special selection for audiogenic seizures has
ever been performed in laboratory mice. Nevertheless,
there are strains highly prone to audiogenic seizure ﬁts
[1, 2]. Strain DBA/2 is the best known among them.
Experiments with the use of a set of 23 recombinant
inbred strains obtained from parental strains DBA/2J
and C57BL/6J have demonstrated that three genes con-
trol audiogenic seizure ﬁts . One of them,
audiogenic seizure prone
), is located between loci
in chromosome 12; another one,
no farther than 8 cM distal to locus
) in chro-
mosome 4. The third gene,
, is linked to locus
in chromosome 7. These genes account for the
largest part of the genetic variation of the character. In
addition, it has been found that genomic imprinting
affects the genetic predisposition to audiogenic seizure
ﬁts in these mice. This complicates genetic analysis,
because the expression of the character strongly
depends on both nonallelic interactions and the origin
of the allele (maternal or paternal).
Audiogenic seizures have also been observed in rats.
They are expressed most strongly in adult rats, in con-
trast to DBA/2J mice, where the seizures only occur
within a narrow age range (between the 16th and 40th
days of life). In rats, no genes responsible for this char-
acter have been mapped. It is unknown whether mice
and rats differ from each other in the genetic control of
audiogenic seizure ﬁts.
Rats are a better object for studying this character
than mice. First, their brain is larger, which makes it
possible, e.g., to analyze the order of the involvement of
different cerebral structures into a seizure ﬁt [4–7]. Sec-
ond, rats, in contrast to mice, have been selected for the
predisposition to audiogenic seizure ﬁts, and several
seizure-prone strains have been obtained [8–10]. These
are, for instance, genetic epilepsy prone strains
obtained from the outbred strain Sprague-
Dowley  in the University of Arizona (United States)
in the late 1950s, strains WAR and KM (Krushinsky–
Molodkina) selected from outbred Wistar rats [10, 11],
and the well-known outbred strain Long–Evans .
We did not ﬁnd any published data on the mode of
inheritance of the predisposition to audiogenic seizure
ﬁts in GEPR3 or GEPR9 rats; however, the existence of
these strain, with GEPR9 being characterized by more
intense seizures than GEPR-3, indicates that the genetic
control of this character is complicated .
The breeding of WAR rats  was accompanied by
rapid changes in the character in response to selection.
Between generations 3 and 17 of selection, the mean
intensity of seizure ﬁts (on an arbitrary point scale)
increased from 37.13 to 83.06 s, and their initial latent
period decreased from 22.82 to 7.84 s. This indicated
an additive control of the character and a weak contri-
bution of gene interaction.
Audiogenic seizures in KM rats have also been stud-
ied in detail. Krushinsky and coworkers began selection
aimed at creating this strain as early as in 1947 . In
the 1980s, the strain was transferred into the inbred
state . At present, almost all KM rats respond to
Genetic Analysis of the Predisposition to Audiogenic Seizure Fits
in Krushinsky–Molodkina Rat Strain
I. B. Fedotova
, Z. A. Kostyna
, I. I. Poletaeva
, V. G. Kolpakov
N. N. Barykina
, and T. I. Axenovich
Moscow State University, Moscow, 119899 Russia; e-mail: email@example.com
Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, 630090 Russia; e-mail: firstname.lastname@example.org
Received February 15, 2005
—The expression of audiogenic seizure ﬁts has been studied in F
hybrids between audiogenic sei-
zure–prone Krushinsky–Molodkina rat strain and Wistar rats not prone to audiogenic seizures, as well as in two
backcross generations. Only 10% of F
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.