Rescue of gamma2 subunit-deficient mice by transgenic overexpression of the GABAA receptor gamma2S or gamma2L subunit isoforms.
The gamma2 subunit is an important functional determinant of GABAA receptors and is essential for formation of high-affinity benzodiazepine binding sites and for synaptic clustering of major GABAA receptor subtypes along with gephyrin. There are two splice variants of the gamma2 subunit, gamma2 short (gamma2S) and gamma2 long (gamma2L), the latter carrying in the cytoplasmic domain an additional eight amino acids with a putative phosphorylation site. Here, we show that transgenic mice expressing either the gamma2S or gamma2L subunit on a gamma2 subunit-deficient background are phenotypically indistinguishable from wild-type. They express nearly normal levels of gamma2 subunit protein and [3H]flumazenil binding sites. Likewise, the distribution, number and size of GABAA receptor clusters colocalized with gephyrin are similar to wild-type in both juvenile and adult mice. Our results indicate that the two gamma2 subunit splice variants can substitute for each other and fulfil the basic functions of GABAA receptors, allowing in vivo studies that address isoform-specific roles in phosphorylation-dependent regulatory mechanisms.
Baer
K
K
Institute of Pharmacology, University of Zurich, Switzerland.
Essrich
C
C
Balsiger
S
S
Wick
M J
MJ
Harris
R A
RA
Fritschy
J M
JM
Lüscher
B
B
D000367:Age Factors; D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis; D002531:Cerebellum / Q000737:chemistry / Q000502:physiology; D005260:Female; D005442:Flumazenil / Q000378:metabolism / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D018757:GABA Modulators / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology; D007536:Isomerism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D010766:Phosphorylation; D011963:Receptors, GABA-A / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D013569:Synapses / Q000737:chemistry; D014316:Tritium
D002352:Carrier Proteins; D018757:GABA Modulators; D008565:Membrane Proteins; D011963:Receptors, GABA-A; C073441:gephyrin; D014316:Tritium; D005442:Flumazenil