Unusual biochemical development of genetically seizure-susceptible El mice

Looking for the 'epilepsy gene', we used ddY derived, genetically seizure-susceptible El mice. To find biochemical abnormalities, we examined the amino acid metabolism and gene activity, including poly(A)+ RNA and sodium channel mRNA expressions, in the developmental growth of El mice. At the early postnatal stage, abnormalities in amino acid metabolism were aberrant free amino acid fluctuations. Almost all free amino acids in the liver of newborn El mice showed considerably lower levels than did ddY mice. Among those amino acids, Asp, Glu and Tyr were extremely low, but rapidly recovered to the ddY level within a week. During the successive growth period, we observed no significant difference in hepatic amino acid levels between El and ddY mice. No such drastic changes were noted in the amino acid levels in the brains of ddY and El mice; only the Gly level was greater in El mice than in ddY mice on the day of birth. Rotatory stimulation which evokes convulsions in El mice but not in ddY mice was applied to adult mice and changes in the amino acid level were assessed. The level of Glu and Tyr in seizure-induced El mice was approximately twice that noted in the liver and brain of El mice, which did not experience seizures. It was also somewhat increased in ddY mice subjected to rotational stress which did not induce seizures in that strain. Gene activity that expresses poly(A)+ RNAs, including sodium channel mRNA, was determined by Northern blot analysis, which reveals unscheduled mRNA synthesis by the appearance of an extra band approximately 3 kb in size.(ABSTRACT TRUNCATED AT 250 WORDS)