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Abstract

The oscillator mouse (Glra1spd-ot) carries a 9 bp microdeletion plus a 2 bp microinsertion in the glycine receptor α1 subunit gene, resulting in the absence of functional α1 polypeptides from the CNS and lethality 3 weeks after birth. Depending on differential use of two splice acceptor sites in exon 9 of the Glra1 gene, the mutant allele encodes either a truncated α1 subunit (spdot-trc) or a polypeptide with a C-terminal missense sequence (spdot-elg). During recombinant expression, both splice variants fail to form ion channels. In complementation studies, a tail construct, encoding the deleted C-terminal sequence, was coexpressed with both mutants. Coexpression with spdot-trc produced glycine-gated ion channels. Rescue efficiency was increased by inclusion of the wild-type motif RRKRRH. In cultured spinal cord neurons from oscillator homozygotes, viral infection with recombinant C-terminal tail constructs resulted in appearance of endogenous α1 antigen. The functional rescue of α1 mutants by the C-terminal tail polypeptides argues for a modular subunit architecture of members of the Cys-loop receptor family.