DEFICIENT DEVELOPMENT AND MAINTENANCE OF POSTSYNAPTIC SPECIALIZATIONSIN MUTANT MICE LACKING AN ADULT ACETYLCHOLINE-RECEPTOR SUBUNIT

At many synapses, 'fetal' neurotransmitter receptor subunits are repla ced by 'adult' subunits as development proceeds. To assess the signifi cance of such transitions, we deleted the gene encoding the adult acet ylcholine receptor (AChR) epsilon subunit, which replaces its fetal co unterpart, the gamma subunit, at the skeletal neuromuscular junction d uring early postnatal life. Several aspects of postnatal maturation, i ncluding synapse elimination, proceeded normally in the absence of the adult AChR, but structural development of the endplate was compromise d. Later, inadequate compensation by the gamma subunit led to severely reduced AChR density in mutant endplates relative to controls. This d ecreased density led to a profound reorganization of AChR-associated c omponents of the postsynaptic membrane and cytoskeleton. Together, the se results suggest novel roles for AChRs in assembly of the postsynapt ic apparatus.