Genetic Study of Cationic ATPase Activities and Audiogenic Seizure Susceptibility in Recombinant Inbred and Congenic Strains of Mice

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Abstract
Total, Mg2+, and Na+,K+-ATPase activities were studied in fresh brain homogenates of the audiogenic seizure (AGS)-resistant C57BL/6J (B6) and AGS-susceptible DBA/2J (D2) inbred strains and in 13 B6 .times. D2 (BXD) recombinant inbred (RI) strains of mice. These activities were also studied in the D2.cntdot.B6-Iasb congenic mice, that are similar genetically to D2 mice, except for the Iasb gene which inhibits the spread of AGS activity. The total and Mg2+ ATPase activities of the brainstem were significantly lower in the D2 than in the B6 mice at 21 days of age. No differences existed between these strains for Na+,K+ ATPase activity. The total, Mg2+, and Na+,K+ ATPase activities in the B6 brainstem did not change noticeably from 21-80 days of age. In the D2 brainstem, the Mg2+ activity increased with age, and the Na+,K+ ATPase activity decreased from 30-80 days of age. No genetic associations were found between AGS susceptibility and total or Mg2+ ATPase activities in the D2.cntdot.B6-Iasb mice or among the 13 BXD RI strains. Differences in genetic background, rather than differences in AGS susceptibility, can account for the lower ATPase activities in 21-day-old D2 mice. The Mg2+ and Na+,K+ ATPase activities appear to be regulated by more than one gene. The utility of RI and congenic strains for testing the biochemical basis of AGS susceptibility in mice is emphasized.