REDUCED SPONTANEOUS ACTIVITY OF MICE DEFECTIVE IN THE EPSILON-4 SUBUNIT OF THE NMDA RECEPTOR-CHANNEL

In an attempt to examine the functional significance of the molecular diversity of the N-methyl-D-aspartate (NMDA) receptor channel, we gene rated mutant mice defective in the epsilon 4 subunit by gene targeting technique. The epsilon 4 subunit mutant mice grew and mated normally. No epsilon 4 subunit protein was detected in the homozygous mutant mi ce, and the amount of the epsilon 4 subunit protein of 155 kDa was red uced in the heterozygous mice. The expressions of the other NMDA recep tor channel subunit mRNAs were not appreciably affected by the mutatio n. The mutant mice exhibited no obvious histological abnormalities in the various brain regions and in the formation of whisker-related neur onal patterns (barrels, barreloids and barrelettes). In an open field test, however, the epsilon 4 subunit mutant mice showed a reduced spon taneous activity. No significant difference was found between the hete rozygous and mutant mice in motor activity and anxiety tests. These re sults suggest that the epsilon 4 subunit of the NMDA receptor channel plays a role in vivo in controlling the spontaneous behavioral activit y.