E1 mice are an animal model of human epilepsy (idiopathic complex partial s
eizures). We have previously demonstrated abrupt poly(A)(+) RNA expression
in liver from 1-day-old El mouse [Mita et al., 1991. Devl. Brain Res. 64, 2
7-35]. In the present study, we constructed a cDNA library of the poly(A)() RNA. By analyzing cDNA clones and nucleotide sequences, we found a clone
that was homologous to a rat gene of s-adenosyl-L-homocysteine hydrolase (E
C 3.3.1.1.) (SAHH) (a key enzyme in the active methyl transfer pathway) and
showed the gene polymorphism/RFLP(PstI) between the epileptic strain, E1,
and the non-epileptic mother strain, ddY, as indicated in a gel electrophor
esis by cleaving 2.6 kb with PstI into 1.9 kb and 0.7 kb fragment bands. F1
(E1 x ddY) showed the heterozygosity. An attempt to determine the mutation
on the genomic SAHH gene in the E1 disclosed a single nucleotide polymorph
ism indicated by a C --> T transition in the 8th intron, by which the PstI
site was created. SAHH enzymatic activity in the liver in 1-day-old E1 mice
was slight (approximately 10%), and in fact was significantly lower than t
hat of the control ddY. Results suggested that the abrupt primary mRNA tran
scribed on the SAHH gene in the liver of 1-day-old E1 mice was processed pa
rtially or incompletely because of the presence of the point mutation in th
e intron. Accordingly, poor energy supply by the insufficient SAHH enzymati
c activity in the brain postnatally may be responsible for epileptogenesis
in this animal model. It is concluded that a single nucleotide SAHH gene po
lymorphism may be associated with epilepsy in El mice. (C) 2001 Elsevier Sc
ience Ltd. All rights reserved.