Dysbindin Deficiency Modifies the Expression of GABA Neuron and Ion Permeation Transcripts in the Developing Hippocampus.
The neurodevelopmental factor dysbindin is required for synapse function and GABA interneuron development. Dysbindin protein levels are reduced in the hippocampus of schizophrenia patients. Mouse dysbindin genetic defects and other mouse models of neurodevelopmental disorders share defective GABAergic neurotransmission and, in several instances, a loss of parvalbumin-positive interneuron phenotypes. This suggests that mechanisms downstream of dysbindin deficiency, such as those affecting GABA interneurons, could inform pathways contributing to or ameliorating diverse neurodevelopmental disorders. Here we define the transcriptome of developing wild type and dysbindin nullBloc1s8sdy/sdymouse hippocampus in order to identify mechanisms downstream dysbindin defects. The dysbindin mutant transcriptome revealed previously reported GABA parvalbumin interneuron defects. However, theBloc1s8sdy/sdytranscriptome additionally uncovered changes in the expression of molecules controlling cellular excitability such as the cation-chloride cotransporters NKCC1, KCC2, and NCKX2 as well as the potassium channel subunits Kcne2 and Kcnj13. Our results suggest that dysbindin deficiency phenotypes, such as GABAergic defects, are modulated by the expression of molecules controlling the magnitude and cadence of neuronal excitability.
Department of Biology, Agnes-Scott College, Decatur, GA, USA.
Jennifer
J
Larimore
Department of Cell Biology, Emory University, Atlanta, GA, USA.
Stephanie A
SA
Zlatic
Department of Biology, Agnes-Scott College, Decatur, GA, USA.
Miranda
M
Arnold
Department of Biology, Agnes-Scott College, Decatur, GA, USA.
Kaela S
KS
Singleton
Department of Biology, Agnes-Scott College, Decatur, GA, USA.
Rebecca
R
Cross
Department of Biology, Agnes-Scott College, Decatur, GA, USA.
Hannah
H
Rudolph
Department of Biology, Agnes-Scott College, Decatur, GA, USA.
Martha V
MV
Bruegge
Department of Biology, Agnes-Scott College, Decatur, GA, USA.
Andrea
A
Sweetman
Department of Biology, Agnes-Scott College, Decatur, GA, USA.
Cecilia
C
Garza
Department of Biology, Agnes-Scott College, Decatur, GA, USA.
Eli
E
Whisnant
Department of Cell Biology, Emory University, Atlanta, GA, USA.
Victor
V
Faundez
BLOC-1; GABA; Neurodevelopmental disorders; dysbindin; parvalbumin