Gene Symbol: Adgrv1
Description: adhesion G protein-coupled receptor V1
Alias: Frings, Gpr98, Mass1, Mgr1, VLGR1, G-protein coupled receptor 98, monogenic audiogenic seizure susceptibility protein 1, monogenic, audiogenic seizure susceptibility 1, neurepin, very large G protein-coupled receptor 1
Species: mouse
Products:     Adgrv1

Top Publications

  1. McMillan D, White P. Loss of the transmembrane and cytoplasmic domains of the very large G-protein-coupled receptor-1 (VLGR1 or Mass1) causes audiogenic seizures in mice. Mol Cell Neurosci. 2004;26:322-9 pubmed
    At approximately 6300 amino acids, very large G-protein-coupled receptor-1 (VLGR1, also termed Mass1) is the largest known cell surface protein...
  2. Michalski N, Michel V, Bahloul A, Lefevre G, Barral J, Yagi H, et al. Molecular characterization of the ankle-link complex in cochlear hair cells and its role in the hair bundle functioning. J Neurosci. 2007;27:6478-88 pubmed
    Several lines of evidence indicate that very large G-protein-coupled receptor 1 (Vlgr1) makes up the ankle links that connect the stereocilia of hair cells at their base...
  3. McGee J, Goodyear R, McMillan D, Stauffer E, Holt J, Locke K, et al. The very large G-protein-coupled receptor VLGR1: a component of the ankle link complex required for the normal development of auditory hair bundles. J Neurosci. 2006;26:6543-53 pubmed the avian ortholog of the very large G-protein-coupled receptor VLGR1, the product of the Usher syndrome USH2C (Mass1) locus. Like ankle links, Vlgr1 is expressed transiently around the base of developing hair bundles in mice...
  4. Yagi H, Takamura Y, Yoneda T, Konno D, Akagi Y, Yoshida K, et al. Vlgr1 knockout mice show audiogenic seizure susceptibility. J Neurochem. 2005;92:191-202 pubmed
    ..b>Vlgr1 (Vlgr1b, Vlgr1d and Vlgr1e) mRNA is expressed predominantly in the neuroepithelium of the developing mouse brain...
  5. Maerker T, Van Wijk E, Overlack N, Kersten F, McGee J, Goldmann T, et al. A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells. Hum Mol Genet. 2008;17:71-86 pubmed
    ..Analyses of Vlgr1/del7TM mice revealed the ectodomain of VLGR1b as a component of fibrous links present in this gap...
  6. Skradski S, Clark A, Jiang H, White H, Fu Y, Ptacek L. A novel gene causing a mendelian audiogenic mouse epilepsy. Neuron. 2001;31:537-44 pubmed
    b>Frings mice are a model of generalized epilepsy and have seizures in response to loud noises. This phenotype is due to the autosomal recessive inheritance of a single gene on mouse chromosome 13...
  7. McMillan D, Kayes Wandover K, Richardson J, White P. Very large G protein-coupled receptor-1, the largest known cell surface protein, is highly expressed in the developing central nervous system. J Biol Chem. 2002;277:785-92 pubmed
    ..We previously identified a member of the G protein-coupled receptor family, very large G protein-coupled receptor-1 (VLGR1)...
  8. Scheel H, Tomiuk S, Hofmann K. A common protein interaction domain links two recently identified epilepsy genes. Hum Mol Genet. 2002;11:1757-62 pubmed
    ..Two apparent exceptions to this rule are the MASS1 gene, which is mutated in the Frings mouse model of audiogenic epilepsy, and the LGI1 gene, which is mutated in autosomal dominant partial epilepsy ..
  9. Zallocchi M, Sisson J, Cosgrove D. Biochemical characterization of native Usher protein complexes from a vesicular subfraction of tracheal epithelial cells. Biochemistry. 2010;49:1236-47 pubmed publisher
    ..This complex(es) is present primarily in transport vesicles at the apical pole of tracheal epithelial cells, predicting that Usher proteins may be directionally transported as complexes in hair cells and photoreceptors. ..

More Information


  1. Van Wijk E, van der Zwaag B, Peters T, Zimmermann U, te Brinke H, Kersten F, et al. The DFNB31 gene product whirlin connects to the Usher protein network in the cochlea and retina by direct association with USH2A and VLGR1. Hum Mol Genet. 2006;15:751-65 pubmed
    ..Our data show that whirlin is connected to the dynamic Usher protein interactome and indicate that whirlin has a pleiotropic function in both the retina and the inner ear. ..
  2. Yagi H, Tokano H, Maeda M, Takabayashi T, Nagano T, Kiyama H, et al. Vlgr1 is required for proper stereocilia maturation of cochlear hair cells. Genes Cells. 2007;12:235-50 pubmed
    ..Its function is unknown, although mice with deletion of Vlgr1 (Vlgr1b together with other splicing variants, Vlgr1c, Vlgr1d and Vlgr1e) are known to exhibit audiogenic seizure ..
  3. Zou J, Luo L, Shen Z, Chiodo V, Ambati B, Hauswirth W, et al. Whirlin replacement restores the formation of the USH2 protein complex in whirlin knockout photoreceptors. Invest Ophthalmol Vis Sci. 2011;52:2343-51 pubmed publisher
    ..Mutations in this gene cause disruption of the USH2 protein complex composed of USH2A and VLGR1 at the periciliary membrane complex (PMC) in photoreceptors...
  4. Skradski S, White H, Ptacek L. Genetic mapping of a locus (mass1) causing audiogenic seizures in mice. Genomics. 1998;49:188-92 pubmed
    b>Frings audiogenic seizure-susceptible mice are a model for sensory-evoked reflex seizures...
  5. Lelli A, Michel V, Boutet de Monvel J, Cortese M, Bosch Grau M, Aghaie A, et al. Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth. J Cell Biol. 2016;212:231-44 pubmed publisher
  6. Zou J, Mathur P, Zheng T, Wang Y, Almishaal A, Park A, et al. Individual USH2 proteins make distinct contributions to the ankle link complex during development of the mouse cochlear stereociliary bundle. Hum Mol Genet. 2015;24:6944-57 pubmed publisher
    ..Our thorough phenotypical characterization of USH2 mouse models is essential for future use of these animal models in therapeutic development. ..
  7. Klein B, Fu Y, Ptacek L, White H. Auditory deficits associated with the frings mgr1 (mass1) mutation in mice. Dev Neurosci. 2005;27:321-32 pubmed
    The gene responsible for the audiogenic seizure (AGS) phenotype in Frings mice, which was identified and originally designated Mass1, is now referred to as Mgr1...
  8. Johnson K, Zheng Q, Weston M, Ptacek L, Noben Trauth K. The Mass1frings mutation underlies early onset hearing impairment in BUB/BnJ mice, a model for the auditory pathology of Usher syndrome IIC. Genomics. 2005;85:582-90 pubmed
    The human ortholog of the gene responsible for audiogenic seizure susceptibility in Frings and BUB/BnJ mice (mouse gene symbol Mass1) recently was shown to underlie Usher syndrome type IIC (USH2C)...
  9. Goodyear R, Jones S, Sharifi L, Forge A, Richardson G. Hair bundle defects and loss of function in the vestibular end organs of mice lacking the receptor-like inositol lipid phosphatase PTPRQ. J Neurosci. 2012;32:2762-72 pubmed publisher
    ..The results reveal a distinct phenotype in the vestibular system of Ptprq(-/-) mice and suggest similar hair bundle defects may underlie the vestibular dysfunction reported in humans with mutations in PTPRQ. ..
  10. Zallocchi M, Meehan D, Delimont D, Rutledge J, Gratton M, Flannery J, et al. Role for a novel Usher protein complex in hair cell synaptic maturation. PLoS ONE. 2012;7:e30573 pubmed publisher
    ..Cadherin-23 (CDH23), protocadherin-15 (PCDH15) and the very large G-protein coupled receptor 1 (VLGR1) have been implicated in the development of cochlear hair cell stereocilia, while clarin-1 has been suggested to ..
  11. Zallocchi M, Delimont D, Meehan D, Cosgrove D. Regulated vesicular trafficking of specific PCDH15 and VLGR1 variants in auditory hair cells. J Neurosci. 2012;32:13841-59 pubmed publisher
    ..mouse cochleae and UB/OC-1 cells were used in this work to address whether specific variants of PCDH15 and VLGR1 are being selectively transported to opposite poles of the hair cells...
  12. Shin D, Lin S, Fu Y, Ptacek L. Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via G?s/G?q-mediated protein kinases A/C. Proc Natl Acad Sci U S A. 2013;110:19101-6 pubmed publisher
    ..A truncating mutation in the Mass1 gene causes autosomal recessive, sound-induced seizures in the Frings mouse. However, the function of MASS1 and the mechanism underlying Frings mouse epilepsy are not known...
  13. Cosgrove D, Zallocchi M. Usher protein functions in hair cells and photoreceptors. Int J Biochem Cell Biol. 2014;46:80-9 pubmed publisher
  14. Schwander M, Sczaniecka A, Grillet N, Bailey J, Avenarius M, Najmabadi H, et al. A forward genetics screen in mice identifies recessive deafness traits and reveals that pejvakin is essential for outer hair cell function. J Neurosci. 2007;27:2163-75 pubmed
  15. Yagi H, Noguchi Y, Kitamura K, Sato M. Deficiency of Vlgr1 resulted in deafness and susceptibility to audiogenic seizures while the degree of hearing impairment was not correlated with seizure severity in C57BL/6- and 129-backcrossed lines of Vlgr1 knockout mice. Neurosci Lett. 2009;461:190-5 pubmed publisher
    b>Vlgr1 (very large G-protein coupled receptor 1) knockout mice against hybrid backgrounds of the 129/Ola and C57BL/6 mouse strains show hearing deficit and high susceptibility to audiogenic seizures...
  16. Klein B, Fu Y, Ptacek L, White H. c-Fos immunohistochemical mapping of the audiogenic seizure network and tonotopic neuronal hyperexcitability in the inferior colliculus of the Frings mouse. Epilepsy Res. 2004;62:13-25 pubmed
    The Frings mouse is a model of audiogenic seizure (AGS) susceptibility. The genetic locus responsible for the AGS phenotype in the Frings mouse has been named monogenic audiogenic seizure-susceptible (MASS1)...
  17. Urano T, Shiraki M, Yagi H, Ito M, Sasaki N, Sato M, et al. GPR98/Gpr98 gene is involved in the regulation of human and mouse bone mineral density. J Clin Endocrinol Metab. 2012;97:E565-74 pubmed publisher
    ..We focused on an SNP of G protein-coupled receptor 98 (GPR98) gene that showed a significant P value after the multiple-comparison tests in Japanese postmenopausal women...
  18. Zou J, Zheng T, Ren C, Askew C, Liu X, Pan B, et al. Deletion of PDZD7 disrupts the Usher syndrome type 2 protein complex in cochlear hair cells and causes hearing loss in mice. Hum Mol Genet. 2014;23:2374-90 pubmed publisher
    ..At the molecular level, PDZD7 determines the localization of the USH2 protein complex, composed of USH2A, GPR98 and WHRN, to ankle links in developing cochlear hair cells, likely through its direct interactions with these ..
  19. Meisler M, Kearney J, Ottman R, Escayg A. Identification of epilepsy genes in human and mouse. Annu Rev Genet. 2001;35:567-88 pubmed
    ..The development of pharmaceuticals directed towards specific epilepsy genotypes can be anticipated, and the introduction of patient mutations into the mouse genome will provide models for testing these targeted therapies. ..
  20. Libé Philippot B, Michel V, Boutet de Monvel J, Le Gal S, Dupont T, Avan P, et al. Auditory cortex interneuron development requires cadherins operating hair-cell mechanoelectrical transduction. Proc Natl Acad Sci U S A. 2017;114:7765-7774 pubmed publisher
    ..In the absence of adhesion G protein-coupled receptor V1 (adgrv1), another hair bundle link protein, the entry of Cdhr23- and Cdhr15-expressing interneuron ..
  21. Chen Q, Zou J, Shen Z, Zhang W, Yang J. Whirlin and PDZ domain-containing 7 (PDZD7) proteins are both required to form the quaternary protein complex associated with Usher syndrome type 2. J Biol Chem. 2014;289:36070-88 pubmed publisher
    ..Among the three USH clinical types, type 2 (USH2) occurs most commonly. USH2A, GPR98, and WHRN are three known causative genes of USH2, whereas PDZD7 is a modifier gene found in USH2 patients...
  22. Sigmund C, Jones C, Jacob H, Ingelfinger J, Kim U, Gamble D, et al. Pathophysiology of vascular smooth muscle in renin promoter-T-antigen transgenic mice. Am J Physiol. 1991;260:F249-57 pubmed
    ..The observed ability of renal vascular cells to be recruited to express both renin and T-antigen suggests a mechanism that can explain the development of the renal pathology in these mice...
  23. Johnson K, Zheng Q, Noben Trauth K. Strain background effects and genetic modifiers of hearing in mice. Brain Res. 2006;1091:79-88 pubmed
    ..This variant also was shown to modify hearing loss associated with the Atp2b2(dfw-2J) and Mass1(frings) mutations...