Genetics, Vol 137, 257-265, Copyright © 1994


INVESTIGATIONS

Genetic Analysis of Nucleotide Triphosphatase Activity in the Mouse Brain

K. M. Allen and T. N. Seyfried
Present address: Neurology Department, Beth Israel Hospital, Harvard Medical School, Warren Alpert Building 347, 200 Longwood Avenue, Boston, Massachusetts 02115.

A Ca(2+)- or Mg(2+)-stimulated ecto-ATPase is thought to regulate the hydrolysis of extracellular ATP in nervous tissues. The hydrolysis of nucleotide triphosphates (NTPs) was analyzed in brain microsomal fractions from crosses of DBA/2J (D2) and C57BL/6J (B6) mice. The nucleotide triphosphatase (NTPase) activity was significantly reduced in D2 mice as compared to B6 mice, and B6D2F(1) hybrids had activities intermediate to the parentals. A significant positive correlation was found between the hydrolysis of four NTPs (ATP, CTP, GTP and UTP) in 24 B6 X D2 (BXD) recombinant inbred (RI) strains of mice and in 80 B6D2F(1) X D2 backcross mice. The RI strains and backcross mice fell into two distinct groups with respect to the NTPase activity. Linkage of NTPase activity was suggested with the chromosome 2 markers, D2Mit6 and Ass-1, in the RI strains, and was confirmed by analysis of other markers in the backcross population. These data suggest that the Ca(2+)- or Mg(2+)-stimulated hydrolysis of NTPs, designated Ntp, is regulated by a single gene located on proximal chromosome 2. Although an association was observed previously between Ca(2+)-ATPase activity and susceptibility to audiogenic seizures (AGS), no significant association was observed for the expression of Ntp and AGS susceptibility.