TY - JOUR
T1 - Loss of the transmembrane and cytoplasmic domains of the very large G-protein-coupled receptor-1 (VLGR1 or Mass1) causes audiogenic seizures in mice
AU - McMillan, D. Randy
AU - White, Perrin C.
N1 - Funding Information:
We thank Kathleen Kayes-Wandover for a RT-PCR experiment, Kyle Anderson for excellent technical assistance, John Shelton and Chris Pomajzl of the Molecular Pathology Core for preparation of embryo sections and in situ hybridizations and images, Christa Hladik of the Pathology Immunohistochemistry Lab for preparation of embryo sections and immunohistochemistry, James Richardson and Steven Goldman for helpful discussions, and Eric Nestler for reviewing the manuscript. PCW is supported by the Audry Newman Rapoport Distinguished Chair in Pediatric Endocrinology. This work received additional support from the Department of Pediatrics at UT Southwestern Medical Center.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/6
Y1 - 2004/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.mcn.2004.02.005
DO - 10.1016/j.mcn.2004.02.005
M3 - Article
C2 - 15207856
AN - SCOPUS:2942633028
SN - 1044-7431
VL - 26
SP - 322
EP - 329
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 2
ER -