 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, October 15, 1998, 18(20):8505-8514
Mice Lacking the
3 Subunit of the GABAA Receptor Have the Epilepsy Phenotype and Many of the Behavioral Characteristics of Angelman Syndrome
T. M. DeLorey1, A. Handforth3, S. G. Anagnostaras2, G. E. Homanics4, B. A. Minassian3, A. Asatourian3, M. S. Fanselow2, A. Delgado-Escueta2, G. D. Ellison2, and R. W. Olsen1 Departments of 1 Molecular and Medical Pharmacology and 2 Psychology, University of California, Los Angeles, California 90095, and 3 Neurology Division, West Los Angeles Veteran's Affairs Medical Center, Los Angeles, California 90073, and 4 Department of Anesthesiology/Critical Care Medicine, University of Pittsburgh, Pennsylvania 15261
Angelman syndrome (AS) is a severe neurodevelopmental disorder resulting from a deletion/mutation in maternal chromosome 15q11-13. The genes in 15q11-13 contributing to the full array of the clinical phenotype are not fully identified. This study examines whether a loss or reduction in the GABAA receptor
3 subunit (GABRB3) gene, contained within the AS deletion region, may contribute to the overall severity of AS. Disrupting the gabrb3 gene in mice produces electroencephalographic abnormalities, seizures, and behavior that parallel those seen in AS. The seizures that are observed in these mice showed a pharmacological response profile to antiepileptic medications similar to that observed in AS. Additionally, these mice exhibited learning and memory deficits, poor motor skills on a repetitive task, hyperactivity, and a disturbed rest-activity cycle, features all common to AS. The loss of the single gene, gabrb3, in these mice is sufficient to cause phenotypic traits that have marked similarities to the clinical features of AS, indicating that impaired expression of the GABRB3 gene in humans probably contributes to the overall phenotype of Angelman syndrome. At least one other gene, the E6-associated protein ubiquitin-protein ligase (UBE3A) gene, has been implicated in AS, so the relative contribution of the GABRB3 gene alone or in combination with other genes remains to be established.
Key words: epilepsy; seizure; Angelman syndrome; GABAA receptor; mouse model; GABRB3; learning and memory; hyperactivity; motor coordination; sleep
Copyright © 1998 Society for Neuroscience 0270-6474/98/18208505-10$05.00/0
This article has been cited by other articles:
H. Hentschke, C. Benkwitz, M. I. Banks, M. G. Perkins, G. E. Homanics, and R. A. Pearce
Altered GABAA,slow Inhibition and Network Oscillations in Mice Lacking the GABAA Receptor {beta}3 Subunit
J Neurophysiol, December 1, 2009; 102(6): 3643 - 3655.
[Abstract] [Full Text] [PDF]
A. C. Need, D. K. Attix, J. M. McEvoy, E. T. Cirulli, K. L. Linney, P. Hunt, D. Ge, E. L. Heinzen, J. M. Maia, K. V. Shianna, et al.
A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB
Hum. Mol. Genet., December 1, 2009; 18(23): 4650 - 4661.
[Abstract] [Full Text] [PDF]
C. M. Houston, Q. He, and T. G. Smart
CaMKII phosphorylation of the GABAA receptor: receptor subtype- and synapse-specific modulation
J. Physiol., May 15, 2009; 587(10): 2115 - 2125.
[Abstract] [Full Text] [PDF]
C. M. Schofield, M. Kleiman-Weiner, U. Rudolph, and J. R. Huguenard
A gain in GABAA receptor synaptic strength in thalamus reduces oscillatory activity and absence seizures
PNAS, May 5, 2009; 106(18): 7630 - 7635.
[Abstract] [Full Text] [PDF]
L. J. Voss, J. W. Sleigh, J. P. M. Barnard, and H. E. Kirsch
The Howling Cortex: Seizures and General Anesthetic Drugs
Anesth. Analg., November 1, 2008; 107(5): 1689 - 1703.
[Abstract] [Full Text] [PDF]
C. M. Houston, A. M. Hosie, and T. G. Smart
Distinct Regulation of {beta}2 and {beta}3 Subunit-Containing Cerebellar Synaptic GABAA Receptors by Calcium/Calmodulin-Dependent Protein Kinase II
J. Neurosci., July 23, 2008; 28(30): 7574 - 7584.
[Abstract] [Full Text] [PDF]
S. M. Sunkin and J. G. Hohmann
Insights from spatially mapped gene expression in the mouse brain
Hum. Mol. Genet., October 15, 2007; 16(R2): R209 - R219.
[Abstract] [Full Text] [PDF]
C. M. Houston, H. H. C. Lee, A. M. Hosie, S. J. Moss, and T. G. Smart
Identification of the Sites for CaMK-II-dependent Phosphorylation of GABAA Receptors
J. Biol. Chem., June 15, 2007; 282(24): 17855 - 17865.
[Abstract] [Full Text] [PDF]
A. Hogart, R. P. Nagarajan, K. A. Patzel, D. H. Yasui, and J. M. LaSalle
15q11-13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders
Hum. Mol. Genet., March 15, 2007; 16(6): 691 - 703.
[Abstract] [Full Text] [PDF]
J. J. Yi and M. D. Ehlers
Emerging Roles for Ubiquitin and Protein Degradation in Neuronal Function
Pharmacol. Rev., March 1, 2007; 59(1): 14 - 39.
[Abstract] [Full Text] [PDF]
S. F. Maison, T. W. Rosahl, G. E. Homanics, and M. C. Liberman
Functional Role of GABAergic Innervation of the Cochlea: Phenotypic Analysis of Mice Lacking GABAA Receptor Subunits {alpha}1, {alpha}2, {alpha}5, {alpha}6, beta2, beta3, or {delta}
J. Neurosci., October 4, 2006; 26(40): 10315 - 10326.
[Abstract] [Full Text] [PDF]
C. M. Borghese, D. F. Werner, N. Topf, N. V. Baron, L. A. Henderson, S. L. Boehm II, Y. A. Blednov, A. Saad, S. Dai, R. A. Pearce, et al.
An Isoflurane- and Alcohol-Insensitive Mutant GABAA Receptor {alpha}1 Subunit with Near-Normal Apparent Affinity for GABA: Characterization in Heterologous Systems and Production of Knockin Mice
J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 208 - 218.
[Abstract] [Full Text] [PDF]
K. D. Valente, C. P. Koiffmann, C. Fridman, M. Varella, F. Kok, J. Q. Andrade, R. M. Grossmann, and M. J. Marques-Dias
Epilepsy in Patients With Angelman Syndrome Caused by Deletion of the Chromosome 15q11-13
Arch Neurol, January 1, 2006; 63(1): 122 - 128.
[Abstract] [Full Text] [PDF]
L. W. J. Bosman, K. Heinen, S. Spijker, and A. B. Brussaard
Mice Lacking the Major Adult GABAA Receptor Subtype Have Normal Number of Synapses, But Retain Juvenile IPSC Kinetics Until Adulthood
J Neurophysiol, July 1, 2005; 94(1): 338 - 346.
[Abstract] [Full Text] [PDF]
R. C. Samaco, A. Hogart, and J. M. LaSalle
Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3
Hum. Mol. Genet., February 15, 2005; 14(4): 483 - 492.
[Abstract] [Full Text] [PDF]
E. M. Cooper, A. W. Hudson, J. Amos, J. Wagstaff, and P. M. Howley
Biochemical Analysis of Angelman Syndrome-associated Mutations in the E3 Ubiquitin Ligase E6-associated Protein
J. Biol. Chem., September 24, 2004; 279(39): 41208 - 41217.
[Abstract] [Full Text] [PDF]
P. Taglialatela, J. M. Soria, V. Caironi, A. Moiana, and S. Bertuzzi
Compromised generation of GABAergic interneurons in the brains of Vax1-/- mice
Development, September 1, 2004; 131(17): 4239 - 4249.
[Abstract] [Full Text] [PDF]
S Baron-Cohen
The cognitive neuroscience of autism
J. Neurol. Neurosurg. Psychiatry, July 1, 2004; 75(7): 945 - 948.
[Full Text] [PDF]
R. Muhle, S. V. Trentacoste, and I. Rapin
The Genetics of Autism
Pediatrics, May 1, 2004; 113(5): e472 - e486.
[Abstract] [Full Text] [PDF]
J. Yun, R. J. Gaivin, D. F. McCune, A. Boongird, R. S. Papay, Z. Ying, P. J. Gonzalez-Cabrera, I. Najm, and D. M. Perez
Gene expression profile of neurodegeneration induced by {alpha}1B-adrenergic receptor overactivity: NMDA/GABAA dysregulation and apoptosis
Brain, December 1, 2003; 126(12): 2667 - 2681.
[Abstract] [Full Text] [PDF]
V. S. Sohal and J. R. Huguenard
Inhibitory Interconnections Control Burst Pattern and Emergent Network Synchrony in Reticular Thalamus
J. Neurosci., October 1, 2003; 23(26): 8978 - 8988.
[Abstract] [Full Text] [PDF]
D. S. Reynolds, T. W. Rosahl, J. Cirone, G. F. O'Meara, A. Haythornthwaite, R. J. Newman, J. Myers, C. Sur, O. Howell, A. R. Rutter, et al.
Sedation and Anesthesia Mediated by Distinct GABAA Receptor Isoforms
J. Neurosci., September 17, 2003; 23(24): 8608 - 8617.
[Abstract] [Full Text] [PDF]
E. Ramadan, Z. Fu, G. Losi, G. E. Homanics, J. H. Neale, and S. Vicini
GABAA Receptor beta 3 Subunit Deletion Decreases alpha 2/3 Subunits and IPSC Duration
J Neurophysiol, January 1, 2003; 89(1): 128 - 134.
[Abstract] [Full Text] [PDF]
R. Borgatti, P. Piccinelli, D. Passoni, A. Romeo, M. Viri, S. A. Musumeci, M. Elia, T. Cogliati, D. Valseriati, R. Grasso, et al.
Peripheral Markers of the {gamma}-Aminobutyric Acid (GABA)ergic System in Angelman's Syndrome
J Child Neurol, January 1, 2003; 18(1): 21 - 25.
[Abstract] [PDF]
J. E. Kralic, E. R. Korpi, T. K. O'Buckley, G. E. Homanics, and A. L. Morrow
Molecular and Pharmacological Characterization of GABAA Receptor alpha 1 Subunit Knockout Mice
J. Pharmacol. Exp. Ther., September 1, 2002; 302(3): 1037 - 1045.
[Abstract] [Full Text] [PDF]
N. Collinson, F. M. Kuenzi, W. Jarolimek, K. A. Maubach, R. Cothliff, C. Sur, A. Smith, F. M. Otu, O. Howell, J. R. Atack, et al.
Enhanced Learning and Memory and Altered GABAergic Synaptic Transmission in Mice Lacking the alpha 5 Subunit of the GABAA Receptor
J. Neurosci., July 1, 2002; 22(13): 5572 - 5580.
[Abstract] [Full Text] [PDF]
C D M van Karnebeek, I van Gelderen, G J Nijhof, N G Abeling, P Vreken, E J Redeker, A M van Eeghen, J M N Hoovers, and R C M Hennekam
An aetiological study of 25 mentally retarded adults with autism
J. Med. Genet., March 1, 2002; 39(3): 205 - 213.
[Full Text]
Z. Nusser, L. M. Kay, G. Laurent, G. E. Homanics, and I. Mody
Disruption of GABAA Receptors on GABAergic Interneurons Leads to Increased Oscillatory Power in the Olfactory Bulb Network
J Neurophysiol, December 1, 2001; 86(6): 2823 - 2833.
[Abstract] [Full Text] [PDF]
C. Sugiura, K. Ogura, M. Ueno, M. Toyoshima, and A. Oka
High-dose ethosuximide for epilepsy in Angelman syndrome: Implication of GABAA receptor subunit
Neurology, October 23, 2001; 57(8): 1518 - 1519.
[Full Text] [PDF]
C. Sur, K. A. Wafford, D. S. Reynolds, K. L. Hadingham, F. Bromidge, A. Macaulay, N. Collinson, G. O'Meara, O. Howell, R. Newman, et al.
Loss of the Major GABAA Receptor Subtype in the Brain Is Not Lethal in Mice
J. Neurosci., May 15, 2001; 21(10): 3409 - 3418.
[Abstract] [Full Text] [PDF]
P. S. Buckmaster, A. L. Jongen-Relo, S. B. Davari, and E. H. Wong
Testing the Disinhibition Hypothesis of Epileptogenesis In Vivo and during Spontaneous Seizures
J. Neurosci., August 15, 2000; 20(16): 6232 - 6240.
[Abstract] [Full Text] [PDF]
J. A. Lamb, J. Moore, A. Bailey, and A. P. Monaco
Autism: recent molecular genetic advances
Hum. Mol. Genet., April 1, 2000; 9(6): 861 - 868.
[Abstract] [Full Text] [PDF]
L. Tarantino and M. Bucan
Dissection of behavior and psychiatric disorders using the mouse as a model
Hum. Mol. Genet., April 1, 2000; 9(6): 953 - 965.
[Abstract] [Full Text] [PDF]
V. S. Sohal, M. M. Huntsman, and J. R. Huguenard
Reciprocal Inhibitory Connections Regulate the Spatiotemporal Properties of Intrathalamic Oscillations
J. Neurosci., March 1, 2000; 20(5): 1735 - 1745.
[Abstract] [Full Text] [PDF]
S. G. Anagnostaras, S. A. Josselyn, P. W. Frankland, and A. J. Silva
Computer-Assisted Behavioral Assessment of Pavlovian Fear Conditioning in Mice
Learn. Mem., January 1, 2000; 7(1): 58 - 72.
[Abstract] [Full Text]
R. M. Mihalek, P. K. Banerjee, E. R. Korpi, J. J. Quinlan, L. L. Firestone, Z.-P. Mi, C. Lagenaur, V. Tretter, W. Sieghart, S. G. Anagnostaras, et al.
Attenuated sensitivity to neuroactive steroids in gamma -aminobutyrate type A receptor delta subunit knockout mice
PNAS, October 26, 1999; 96(22): 12905 - 12910.
[Abstract] [Full Text] [PDF]
Y. Marahrens
X-inactivation by chromosomal pairing events
Genes & Dev., October 15, 1999; 13(20): 2624 - 2632.
[Full Text]
M. R. W. Mann and MarisaS. Bartolomei
Towards a molecular understandingof Prader-Willi and Angelman syndromes
Hum. Mol. Genet., September 1, 1999; 8(10): 1867 - 1873.
[Abstract] [Full Text] [PDF]
N. G. C. Smith and L. D. Hurst
The Causes of Synonymous Rate Variation in the Rodent Genome: Can Substitution Rates Be Used to Estimate the Sex Bias in Mutation Rate?
Genetics, June 1, 1999; 152(2): 661 - 673.
[Abstract] [Full Text]
M. M. Huntsman, D. M. Porcello, G. E. Homanics, T. M. DeLorey, and J. R. Huguenard
Reciprocal Inhibitory Connections and Network Synchrony in the Mammalian Thalamus
Science, January 22, 1999; 283(5401): 541 - 543.
[Abstract] [Full Text]
G. Strous and R Govers
The ubiquitin-proteasome system and endocytosis
J. Cell Sci., January 5, 1999; 112(10): 1417 - 1423.
[Abstract] [PDF]
G. D. Ferguson, S. G. Anagnostaras, A. J. Silva, and H. R. Herschman
Deficits in memory and motor performance in synaptotagmin IV mutant mice
PNAS, May 9, 2000; 97(10): 5598 - 5603.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|