Over-expression of δC-DCLK-short in mouse brain results in a more anxious behavioral phenotype.
Products of the Doublecortin-Like Kinase (DCLK) gene are associated with cortical migration and hippocampal maturation during embryogenesis. However, the functions of those DCLK gene transcripts that encode kinases and are expressed during adulthood are incompletely understood. To elucidate potential functions of these DCLK gene splice variants we have generated and analyzed transgenic mice with neuronal over-expression of a truncated, constitutively active form of DCLK-short, designated δC-DCLK-short. Previously, we have performed an extensive molecular characterization of these transgenic δC-DCLK-short mice and established that a specific subunit of the GABA(A) receptor, which is involved in anxiety-related GABAergic neurotransmission, is down-regulated in the hippocampus. Here we show that δC-DCLK-short mRNA is highly expressed in the hippocampus, cortex and amygdala of transgenic mice. We provide evidence that the δC-DCLK-short protein is expressed and functional. In addition, we examined anxiety-related behavior in δC-DCLK-short mice in the elevated plus maze. Interestingly, δC-DCLK-short mice spend less time, move less in the open arms of the maze and show a reduction in the number of rim dips. These behaviors indicate that δC-DCLK-short mice display a more anxious behavioral phenotype.
Schenk
Geert J
GJ
Division of Medical Pharmacology, Leiden/Amsterdam Centre for Drug Research, Einsteinweg 55, 2300 RA Leiden, The Netherlands. g.j.schenk@LACDR.leidenuniv.nl
Veldhuisen
Barbera
B
Wedemeier
Olga
O
McGown
Caroline C
CC
Schouten
Theo G
TG
Oitzl
Melly
M
de Kloet
E Ron
ER
Vreugdenhil
Erno
E
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D000089742:Doublecortin-Like Kinases; D005106:Exploratory Behavior / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D005818:Genetic Engineering / Q000379:methods; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014018:Tissue Distribution
D010446:Peptide Fragments; D012333:RNA, Messenger; D000089742:Doublecortin-Like Kinases; C485525:Dclk1 protein, mouse; D017346:Protein Serine-Threonine Kinases