Loss of the transmembrane and cytoplasmic domains of the very large G-protein-coupled receptor-1 (VLGR1 or Mass1) causes audiogenic seizures in mice

D. Randy McMillan, Perrin C. White

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

At approximately 6300 amino acids, very large G-protein-coupled receptor-1 (VLGR1, also termed Mass1) is the largest known cell surface protein. It is expressed at high levels within the embryonic nervous system, especially the ventricular zone. A naturally occurring nonsense mutation in VLGR1, V2250X, is linked with susceptibility to audiogenic seizures in mice. Interpretation of this finding is complicated by the existence of splice and transcriptional variants. We targeted the transmembrane and cytoplasmic domains of VLGR1, yielding a gene encoding the complete ectodomain of VLGR1 fused to antigenic tags (VLGR/del7TM). Homozygous mutant mice are susceptible to audiogenic seizures. Western blots detect a single very high molecular weight protein in brain extracts from VLGR/del7TM mice. These findings suggest that loss of VLGR1 transmembrane and cytoplasmic domains underlies the seizure phenotype in both mutant mouse strains, perhaps by disrupting signals regulating neural development.

Original languageEnglish (US)
Pages (from-to)322-329
Number of pages8
JournalMolecular and Cellular Neuroscience
Volume26
Issue number2
DOIs
StatePublished - Jun 2004

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G-Protein-Coupled Receptors
Seizures
Mutant Strains Mice
Nonsense Codon
Nervous System
Membrane Proteins
Molecular Weight
Western Blotting
Phenotype
Amino Acids
Brain
Genes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

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